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Information on EC 6.1.1.4 - leucine-tRNA ligase
for references in articles please use BRENDA:EC6.1.1.4
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EC Tree 6 Ligases
6.1 Forming carbon-oxygen bonds
6.1.1 Ligases forming aminoacyl-tRNA and related compounds
6.1.1.4 leucine-tRNA ligase
The enzyme appears in viruses and cellular organisms
- 6.1.1.4
- aminoacyl-trna
- synthetases
- aminoacylation
-
fidelity
-
leucylation
-
aarss
-
mischarged
-
post-transfer
- norvaline
-
perrault
-
anticodon
- aeolicus
-
isoacceptors
-
misactivated
-
aquifex
- ilers
-
noncognate
- valrs
-
benzoxaborole
-
isoleucyl-trna
-
misaminoacylated
- hsd17b4
-
kmsks
- metrs
-
pour
- trnaser
-
clinique
- trnaleuuur
- valyl-trna
-
isoleucyl
-
trna-dependent
-
pre-transfer
- drug development
- medicine
showSynonyms
leurs, leucyl-trna synthetase, lars2, lars1, ecleurs, cytoplasmic leurs, alphabeta-leurs, glleurs, hs mt leurs, leucyl-trna synthetase 1, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
AaLeuRS
HcleuRS
LARS
LARS1
LARS2
Leucine translase
Leucine--tRNA ligase
Leucyl-transfer ribonucleate synthetase
Leucyl-transfer ribonucleic acid synthetase
Leucyl-transfer RNA synthetase
Leucyl-tRNA synthetase
LeuRS
LeuRS1
LeuRS2
LeuRSTT
leuS
LRS
MmLeuRS
PhLeuRS
Synthetase, leucyl-transfer ribonucleate
additional information
Leucine translase
-
-
-
-
Leucine translase
-
-
Leucine--tRNA ligase
-
-
-
-
Leucine--tRNA ligase
-
-
Leucyl-transfer ribonucleate synthetase
-
-
-
-
Leucyl-transfer ribonucleate synthetase
-
-
Leucyl-transfer ribonucleic acid synthetase
-
-
-
-
Leucyl-transfer ribonucleic acid synthetase
-
-
Leucyl-transfer RNA synthetase
-
-
-
-
Leucyl-transfer RNA synthetase
-
-
Leucyl-tRNA synthetase
-
-
-
-
Leucyl-tRNA synthetase
-
-
Leucyl-tRNA synthetase
-
-
Leucyl-tRNA synthetase
Pyrococcus horikoshii ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3
-
-
LeuRS
-
-
-
-
LeuRS
-
-
LeuRS1
-
isoform, exhibits much higher aminoacylation and editing activity than isoform LeuRS2
LeuRS1
-
isoform, exhibits much higher aminoacylation and editing activity than isoform LeuRS2
-
LeuRS2
-
isoform, exhibits much less aminoacylation and editing activity than isoform LeuRS1
LeuRS2
-
isoform, exhibits much less aminoacylation and editing activity than isoform LeuRS1
-
Synthetase, leucyl-transfer ribonucleate
-
-
-
-
Synthetase, leucyl-transfer ribonucleate
-
-
additional information
-
the enzyme belongs to the class Ia aminoacyl-tRNA transferases
additional information
enzyme belongs to the XUX aminoacyl synthetase family
additional information
-
the enzyme belongs to the class I aminoacyl-tRNA synthetases
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + L-leucine + tRNALeu = AMP + diphosphate + L-leucyl-tRNALeu
bi uni uni bi ping-pong mechanism with ordered addition of ATP and leucine and random release of AMP and leucyl-tRNALeu
-
ATP + L-leucine + tRNALeu = AMP + diphosphate + L-leucyl-tRNALeu
each amino acid is bound through its carboxyl group to the terminal nucleotide (2'- or 3'-hydroxyl end) of specific polynucleotide chains
-
ATP + L-leucine + tRNALeu = AMP + diphosphate + L-leucyl-tRNALeu
ATP and tRNA are bound to the enzyme in almost random order, and diphosphate is dissociated before the rate-limiting step
-
ATP + L-leucine + tRNALeu = AMP + diphosphate + L-leucyl-tRNALeu
Asp345 is involved in the editing process, mechanism of hydrolysis
-
ATP + L-leucine + tRNALeu = AMP + diphosphate + L-leucyl-tRNALeu
Asp419 is involved in the editing process, mechanism of hydrolysis
-
ATP + L-leucine + tRNALeu = AMP + diphosphate + L-leucyl-tRNALeu
active site structure and mechanism, the editing active site binds the two different substrates using a single amino acid discriminatory pocket while preserving he same mode of adenine recognition, Asp347 is involved in the editing process, mechanism of hydrolysis
ATP + L-leucine + tRNALeu = AMP + diphosphate + L-leucyl-tRNALeu
residue E292 is important for aminoacylation activity
-
ATP + L-leucine + tRNALeu = AMP + diphosphate + L-leucyl-tRNALeu
-
-
-
-
ATP + L-leucine + tRNALeu = AMP + diphosphate + L-leucyl-tRNALeu
recognition of the tRNALeu requires the discriminator base A73 and the long variable arm of appropriate stem length, especially the Haloferax volcanii-specific loop sequence A47CG47D and U47H at the base of the helix
-
ATP + L-leucine + tRNALeu = AMP + diphosphate + L-leucyl-tRNALeu
A293 is important for the stability of the enzyme conformation and the editing function and probably is involved in the ATP binding
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Aminoacylation
esterification
Aminoacylation
-
-
-
-
esterification
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
BRENDA
MetaCyc
tRNA charging
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SYSTEMATIC NAME
IUBMB Comments
L-leucine:tRNALeu ligase (AMP-forming)
-
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CAS REGISTRY NUMBER
COMMENTARY
9031-15-6
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2'-dATP + L-leucine + tRNALeu
2'-dAMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
Products: -
Products: -
?
8-azaadenosine 5'-triphosphate + L-leucine + tRNALeu
8-azaadenosine 5'-monophosphate + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
Products: -
Products: -
?
8-bromoadenosine 5'-triphosphate + L-leucine + tRNALeu
8-bromoadenosine 5'-monophosphate + diphosphate + L-leucyl-tRNALeu
8-methylaminoadenosine 5'-triphosphate + L-leucine + tRNALeu
8-methylaminoadenosine 5'-monophosphate + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
Products: -
Products: -
?
Adenosine 5'-O-(3-thio)triphosphate + L-leucine + tRNALeu
adenosine 5'-monophosphate + thiodiphosphate + L-leucyl-tRNALeu
Adenylyl beta,gamma-imido diphosphonate + L-leucine + tRNALeu
Adenylic acid + imido-diphosphate + L-leucyl-tRNALeu
AMP + diphosphate + Ile-tRNALeu
ATP + L-isoleucine + tRNALeu
Substrates: -
Products: -
Products: -
?
AMP + diphosphate + L-leucyl-Pyrococcus horikoshii tRNALeu(GAG)
ATP + L-leucine + Pyrococcus horikoshii tRNALeu(GAG)
ATP + 2-butynylalanine + tRNALeu
AMP + diphosphate + 2-butynylalanyl-tRNALeu
-
Substrates: aminoacylation by mutant T252Y
Products: -
Products: -
?
ATP + allylglycine + tRNALeu
AMP + diphosphate + allylglycyl-tRNALeu
-
Substrates: aminoacylation by mutant T252Y
Products: -
Products: -
?
ATP + homoallylglycine + tRNALeu
AMP + diphosphate + homoallylglycyl-tRNALeu
-
Substrates: aminoacylation by mutant T252Y
Products: -
Products: -
?
ATP + homopropargylglycine + tRNALeu
AMP + diphosphate + homopropargylglycyl-tRNALeu
-
Substrates: aminoacylation by mutant T252Y
Products: -
Products: -
?
ATP + L-didehydroleucine + tRNALeu
AMP + diphosphate + didehydroleucyl-tRNALeu
-
Substrates: reaction is catalyzed by mutant T252Y, not by wild-type
Products: -
Products: -
?
ATP + L-isoleucine + 2'-deoxaadenosine-tRNALeu
AMP + ?
-
Substrates: 2'-deoxyadenosine-tRNA clearly stimulates AMP production in the presence of isoleucine, but not the cognate leucine substrate
Products: -
Products: -
?
ATP + L-leucine + Natrialba magadii tRNALeu(CAA)
AMP + diphosphate + L-leucyl-Natrialba magadii tRNALeu(CAA)
ATP + L-leucine + Natrialba magadii tRNALeu(GAG)
AMP + diphosphate + L-leucyl-Natrialba magadii tRNALeu(GAG)
ATP + L-leucine + Pyrococcus horikoshii tRNALeu(GAG)
AMP + diphosphate + L-leucyl-Pyrococcus horikoshii tRNALeu(GAG)
ATP + L-leucine + tRNACAGLeu
AMP + diphosphate + L-leucyl-tRNACAGLeu
Substrates: human cytoplasmic tRNACAGLeu (hctRNACAG)
Products: -
Products: -
?
ATP + L-leucine + tRNAIle
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
Products: -
Products: -
?
ATP + L-leucine + tRNALeu from Aquifex aeolicus
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
Products: -
Products: -
?
ATP + L-leucine + tRNALeu from Escherichia coli
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
Products: -
Products: -
?
ATP + L-leucine + tRNALeu(UAA)
AMP + diphosphate + L-leucyl-tRNALeu(UAA)
-
Substrates: -
Products: -
Products: -
?
ATP + L-leucine + tRNALeu(UAG)
AMP + diphosphate + L-leucyl-tRNALeu(UAG)
-
Substrates: -
Products: -
Products: -
?
ATP + L-leucine + tRNALeu(UUR)
AMP + diphosphate + L-leucyl-tRNALeu(UUR)
-
Substrates: leucyl-tRNA synthetase contacts tRNALeu(UUR) in the amino acid acid acceptor stem, the anticodon stem, and the D-loop
Products: -
Products: -
?
ATP + L-leucine + tRNALeuA35G
AMP + diphosphate + L-leucyl-tRNALeuA35G
-
Substrates: -
Products: -
Products: -
?
ATP + L-leucine + tRNALeuA73
AMP + diphosphate + L-leucyl-tRNALeuA73
-
Substrates: class II tRNALeu, recognition requires the discriminator base A73 and the long variable arm of appropriate stem length, especially the specific loop sequence A47CG47D and U47H at the base of the helix
Products: -
Products: -
?
ATP + L-leucine + tRNALeuA73G
AMP + diphosphate + L-leucyl-tRNALeuA73G
-
Substrates: -
Products: -
Products: -
?
ATP + L-leucine + tRNALeuGAG
AMP + diphosphate + L-leucyl-tRNALeuGAG
-
Substrates: -
Products: -
Products: -
?
ATP + L-leucine + tRNALeuU73
AMP + diphosphate + L-leucyl-tRNALeuU73
-
Substrates: class II tRNALeu isoacceptor, 17fold lower activity compared to tRNALeuA73
Products: -
Products: -
?
ATP + L-leucine + tRNASer mutant
AMP + diphosphate + L-leucyl-tRNASer mutant
-
Substrates: transplantation of both the discriminator base and the variable arm of tRNALeu are not sufficient to introduce leucylation activity to tRNASer, but additional insertion of additional a nucleotide into the D-loop, which is not involved in the direct interaction with the enzyme, converts tRNASer to an efficient leucine acceptor
Products: -
Products: -
?
ATP + L-leucine + tRNAUAALeu
AMP + diphosphate + L-leucyl-tRNAUAALeu
Substrates: Mycoplasma mobile MmtRNAUAALeu (Mmt-RNAUAALeu)
Products: -
Products: -
?
ATP + L-norisoleucine + tRNALeu
AMP + diphosphate + L-norisoleucyl-tRNALeu
-
Substrates: aminoacylation by mutant T252Y
Products: -
Products: -
?
ATP + L-oxonorvaline + tRNALeu
AMP + diphosphate + oxonorvalyl-tRNALeu
-
Substrates: reaction is catalyzed by mutant T252Y, not by wild-type
Products: -
Products: -
?
L-isoleucyl-tRNALeu + H2O
t-RNALeu + isoleucine
-
Substrates: -
Products: editing activity
Products: editing activity
?
L-isoleucyl-tRNALeu + H2O
t-RNALeu + L-isoleucine
Substrates: -
Products: editing activity
Products: editing activity
?
tubercidin 5'-triphosphate + L-leucine + tRNALeu
tubercidin 5'-phosphate + diphosphate + L-leucyl-tRNALeu
3'-dATP + L-leucine + tRNALeu
3'-dAMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
Products: -
Products: -
?
3'-dATP + L-leucine + tRNALeu
3'-dAMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
Products: -
Products: -
?
3'-dATP + L-leucine + tRNALeu
3'-dAMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
Products: -
Products: -
?
8-bromoadenosine 5'-triphosphate + L-leucine + tRNALeu
8-bromoadenosine 5'-monophosphate + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
Products: -
Products: -
?
8-bromoadenosine 5'-triphosphate + L-leucine + tRNALeu
8-bromoadenosine 5'-monophosphate + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
Products: -
Products: -
?
Adenosine 5'-O-(3-thio)triphosphate + L-leucine + tRNALeu
adenosine 5'-monophosphate + thiodiphosphate + L-leucyl-tRNALeu
-
Substrates: -
Products: -
Products: -
?
Adenosine 5'-O-(3-thio)triphosphate + L-leucine + tRNALeu
adenosine 5'-monophosphate + thiodiphosphate + L-leucyl-tRNALeu
-
Substrates: -
Products: -
Products: -
?
Adenylyl beta,gamma-imido diphosphonate + L-leucine + tRNALeu
Adenylic acid + imido-diphosphate + L-leucyl-tRNALeu
-
Substrates: -
Products: -
Products: -
?
Adenylyl beta,gamma-imido diphosphonate + L-leucine + tRNALeu
Adenylic acid + imido-diphosphate + L-leucyl-tRNALeu
-
Substrates: -
Products: -
Products: -
?
AMP + diphosphate + L-leucyl-Pyrococcus horikoshii tRNALeu(GAG)
ATP + L-leucine + Pyrococcus horikoshii tRNALeu(GAG)
-
Substrates: -
Products: -
Products: -
r
AMP + diphosphate + L-leucyl-Pyrococcus horikoshii tRNALeu(GAG)
ATP + L-leucine + Pyrococcus horikoshii tRNALeu(GAG)
-
Substrates: -
Products: -
Products: -
r
ATP + L-isoleucine + tRNALeu
AMP + diphosphate + L-isoleucyl-tRNALeu
-
Substrates: -
Products: -
Products: -
?
ATP + L-isoleucine + tRNALeu
AMP + diphosphate + L-isoleucyl-tRNALeu
-
Substrates: mutant D345A, not the wild-type which performs only the misacetylation with isoleucine, but eliminates the incorrect isoleucyl-AMP
Products: -
Products: -
r
ATP + L-isoleucine + tRNALeu
AMP + diphosphate + L-isoleucyl-tRNALeu
-
Substrates: wild-type and CP1 domain mutant enzyme, the mischarged product can be edited by the wild-type enzyme, but not by a recombinant isolated CP1 domain
Products: -
Products: -
?
ATP + L-isoleucine + tRNALeu
AMP + diphosphate + L-isoleucyl-tRNALeu
-
Substrates: activity with mutant enzymes T252E and T252D, no activity with wild-type enzyme and with mutant enzyme T252G
Products: -
Products: -
?
ATP + L-isoleucine + tRNALeu
AMP + diphosphate + L-isoleucyl-tRNALeu
-
Substrates: the ratio of turnover number to KM-value for L-leucine is 1600fold higher than the ratio observed for L-isoleucine
Products: -
Products: -
?
ATP + L-isoleucine + tRNALeu
AMP + diphosphate + L-isoleucyl-tRNALeu
-
Substrates: -
Products: -
Products: -
?
ATP + L-isoleucine + tRNALeu
AMP + diphosphate + L-isoleucyl-tRNALeu
-
Substrates: -
Products: -
Products: -
?
ATP + L-isoleucine + tRNALeu
AMP + diphosphate + L-isoleucyl-tRNALeu
-
Substrates: the ratio of turnover number to KM-value for L-leucine is 3000fold higher than the ratio observed for L-isoleucine
Products: -
Products: -
?
ATP + L-isoleucine + tRNALeu
AMP + diphosphate + L-isoleucyl-tRNALeu
-
Substrates: -
Products: -
Products: -
?
ATP + L-isoleucine + tRNALeu
AMP + diphosphate + L-isoleucyl-tRNALeu
Substrates: -
Products: -
Products: -
?
ATP + L-isoleucine + tRNALeu
AMP + diphosphate + L-isoleucyl-tRNALeu
-
Substrates: -
Products: -
Products: -
?
ATP + L-isoleucine + tRNALeu
AMP + diphosphate + L-isoleucyl-tRNALeu
-
Substrates: activity with mutant enzyme D332A, no activity with wild-type full-length enzyme
Products: -
Products: -
?
ATP + L-isoleucine + tRNALeu
AMP + diphosphate + L-isoleucyl-tRNALeu
-
Substrates: mutant D419A, not the wild-type, which performs only the misacetylation with isoleucine, but eliminates the incorrect isoleucyl-AMP
Products: -
Products: -
r
ATP + L-isoleucine + tRNALeu
AMP + diphosphate + L-isoleucyl-tRNALeu
Substrates: -
Products: -
Products: -
?
ATP + L-isoleucine + tRNALeu
AMP + diphosphate + L-isoleucyl-tRNALeu
Substrates: mutant D345A, not the wild-type which performs only the misacetylation with isoleucine, but eliminates the incorrect isoleucyl-AMP
Products: -
Products: -
r
ATP + L-leucine + Natrialba magadii tRNALeu(CAA)
AMP + diphosphate + L-leucyl-Natrialba magadii tRNALeu(CAA)
-
Substrates: -
Products: -
Products: -
?
ATP + L-leucine + Natrialba magadii tRNALeu(CAA)
AMP + diphosphate + L-leucyl-Natrialba magadii tRNALeu(CAA)
-
Substrates: -
Products: -
Products: -
?
ATP + L-leucine + Natrialba magadii tRNALeu(GAG)
AMP + diphosphate + L-leucyl-Natrialba magadii tRNALeu(GAG)
-
Substrates: highest activity
Products: -
Products: -
?
ATP + L-leucine + Natrialba magadii tRNALeu(GAG)
AMP + diphosphate + L-leucyl-Natrialba magadii tRNALeu(GAG)
-
Substrates: highest activity
Products: -
Products: -
?
ATP + L-leucine + Pyrococcus horikoshii tRNALeu(GAG)
AMP + diphosphate + L-leucyl-Pyrococcus horikoshii tRNALeu(GAG)
-
Substrates: 100% activity
Products: -
Products: -
r
ATP + L-leucine + Pyrococcus horikoshii tRNALeu(GAG)
AMP + diphosphate + L-leucyl-Pyrococcus horikoshii tRNALeu(GAG)
-
Substrates: 100% activity
Products: -
Products: -
r
ATP + L-leucine + tRNACAALeu
AMP + diphosphate + L-leucyl-tRNAUAALeu
Substrates: Mycoplasma mobile tRNACAALeu (MmtRNACAALeu) and mutat derivatives
Products: -
Products: -
?
ATP + L-leucine + tRNACAALeu
AMP + diphosphate + L-leucyl-tRNAUAALeu
[Mycoplasma] mobile ATCC 43663 / 163K / NCTC 11711
Substrates: Mycoplasma mobile tRNACAALeu (MmtRNACAALeu) and mutat derivatives
Products: -
Products: -
?
ATP + L-leucine + tRNAGAGLeu
AMP + diphosphate + L-leucyl-tRNAGAGLeu
Substrates: Aquifex aeolicus tRNAGAGLeu (AatRNAGAGLeu)
Products: -
Products: -
?
ATP + L-leucine + tRNAGAGLeu
AMP + diphosphate + L-leucyl-tRNAGAGLeu
Substrates: Escherichia coli tRNAGAGLeu (Ect-RNAGAGLeu)
Products: -
Products: -
?
ATP + L-leucine + tRNAGAGLeu
AMP + diphosphate + L-leucyl-tRNAGAGLeu
Substrates: Pyrococcus horikoshii tRNAGAGLeu (PhtRNAGAGLeu)
Products: -
Products: -
?
ATP + L-leucine + tRNAGAGLeu
AMP + diphosphate + L-leucyl-tRNAGAGLeu
Pyrococcus horikoshii ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3
Substrates: Pyrococcus horikoshii tRNAGAGLeu (PhtRNAGAGLeu)
Products: -
Products: -
?
ATP + L-leucine + tRNALeu
?
-
Substrates: esterifies L-leucine to the cognate tRNA in the initial step of protein biosynthesis
Products: -
Products: -
?
ATP + L-leucine + tRNALeu
?
-
Substrates: mitochondrial enzyme is involved in protein synthesis and mRNA splicing
Products: -
Products: -
?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: enzyme activity only appears when both gene products, of leuS and leuS', coexist
Products: -
Products: -
?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: the cross-species-specific recognition occurs at the alpha-subunit, tRNALeu substrates from Escherichia coli and Aquifex aeolicus
Products: -
Products: -
?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: tRNALeu from Aquifex aeolicus and Escherichia coli, native and recombinant wild-type, the recombinant isolated beta-subunit is inactive in catalysis
Products: -
Products: -
?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: two-step reaction, the beta-subunit alone is responsible for cognate tRNA recognition, enzyme activity requires both subunits
Products: -
Products: -
?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
Products: -
Products: -
?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: two distinct domains of the beta subunit of Aquifex aeolicus leucyl-tRNA synthetase are involved in tRNA binding as revealed by a three-hybrid selection
Products: -
Products: -
?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
Products: -
Products: -
?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: the enzyme hydrolyzes mischarged tRNAs through a post-transfer editing mechanism, the enzyme from Aquifex aeolicus edits the complete set of aminoacylated tRNAs generated by the three enzymes, leucyl-, isoleucyl-, and valyl-tRNA synthetases: Ile-tRNAIle, Val-tRNAIle, ValtRNAVal, Thr-tRNAVal, and Ile-tRNALeu, model of a primitive editing system containing a composite minihelix carrying the triple leucine, isoleucine, and valine identity mimicking the primitive tRNA precursor, overview
Products: -
Products: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
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Substrates: recombinant tRNALeu substrate, two peptides of eight and nine amino acid residues in the domain located in the alpha subunit are essential for the enzymes activity
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
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Substrates: recognition of tRNALeu by the leucyl-tRNA synthetase (LeuRS) is studied by RNA probing and mutagenesis. Results show that the base A73, the core structure of tRNA formed by the tertiary interactions U8-A14, G18-U55 and G19-C56, and the orientation of the variable arm are critical elements for tRNALeu aminoacylation. Although dispensable for aminoacylation, the anticodon arm carries discrete editing determinants that are required for stabilizing the conformation of the post-transfer editing state and for promoting translocation of the tRNA acceptor arm from the synthetic to the editing site
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
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Substrates: the reaction catalyzed by the enzyme plays an important role in the transport of aminoacylated tRNAs from the nucleus to the cytoplasm
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
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Substrates: apart from the homologous substrate the enzyme is able to aminoacylate pure E. coli tRNALeu
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
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Substrates: apart from the homologous substrate the enzyme is able to aminoacylate pure E. coli tRNALeu
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: r
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: mutant T252A edits correctly charged Leu-tRNALeu
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: the connecting peptide CP1 domain is crucial for the editing function
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: the peptide bond between Glu292 and Ala293 in the large connecting polypeptide CP1 is essential for activity
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
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Substrates: tRNALeu substrates from Escherichia coli and Aquifex aeolicus
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
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Substrates: two-step reaction, the connecting peptide CP1 domain is crucial for the editing function
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
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Substrates: two-step reaction, the first step is reversible, the second is not, tRNA discrimination by a double-sieve mechansim
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: it is proposed that the enzyme uses a lock-and-key mechanism to recognize and discriminate the amino acids
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
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Substrates: two functions of the enzyme in splicing and aminoacylation in vivo, overview
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
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Substrates: a two-step reaction, the first of which, the amino acid activation step, is reversible, while the second aminoacylation step is not, the amino acid editing site for LeuRS resides within the homologous CP1 domain, some positions are idiosyncratic to LeuRS including a conserved arginine conferring amino acid substrate recognition, it complements other sites in the amino acid binding pocket of the editing active site of Escherichia coli LeuRS, including Thr252 and Val338, the latter is second to the first, which collectively fine-tune amino acid specificity to confer fidelity, editing mechanism, residues Arg249, Asp251, Thr252, Met336, and Val338 are involved, overview
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
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Substrates: L570 strongly impacts aminoacylation in two ways: it affects both amino acid discrimination and tRNA binding, overview
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
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Substrates: a two step reaction, the first of which is reversible, overview, the unique inserted leucine-specific domain of LeuRS is required for aminoacylation and not amino acid editing, the domain interacts with the tRNA during amino acid activation and/or tRNA aminoacylation, it might aid the dynamic translocation process that moves tRNA from the aminoacylation to the editing complex, overview
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
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Substrates: the editing domain called CP1 is required for hydrolyzing the incorrectly misaminoacylated noncognate amino acids Ile and Val, the beta-strands, which link the CP1 domain to the aminoacylation core of LeuRS, are required for editing of mischarged tRNALeu, hydrolytic activity is also enhanced by inclusion of short flexible peptides, called hinges, at the end of both LeuRS beta-strands, overview
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: substrate is tRNALeuTAA, overexpressed in and purified from Escherichia coli
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
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Substrates: chloroplastic enzyme: high specificity towards tRNAs, in contrast the cytoplasmic enzyme recognizes tRNAs from the bleached mutant and from yeast, but also some tRNALeu isoacceptors from E. coli
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: tRNAs from Homo sapiens and Giardia lamblia
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: tRNALeu substrate from Escherichia coli, 2-step reaction, the first step is reversible, while the second step is not
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
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Substrates: human cytosolic leucyl-tRNA synthetase is one component of a macromolecular aminoacyl-tRNA synthetase complex. The C-terminal peptide of hcLeuRS is critical for the interaction with hcArgRS and the interaction in the multi-tRNA synthetase complex
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: human mitochondrial LeuRS achieves high aminoacylation fidelity without a functional editing active site, representing a rare example of a class I aminoacyl-tRNA synthetase that does not proofread its products, K600 strongly impacts aminoacylation in two ways: it affects both amino acid discrimination and tRNA binding, overview
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: a complex between prolyl-tRNA synthetase, ProRS, and LeuRS in Methanothermobacter thermautotrophicus enhances tRNAPro aminoacylation, overview
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: cytoplasmic enzyme shows less strict specificity towards tRNA than the chloroplastic enzyme
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: a two step reaction, the C-terminal domain recognizes the long variable arm of tRNALeu for aminoacylation, and the so-called editing domain deacylates incorrectly formed Ile-tRNALeu, structural superposition of tRNAIle onto the LeuRS-tRNALeu complex indicated that Ile911, Lys912, and Glu913 of the LeuRS C-terminal domain clash with U20 of tRNAIle, which is bulged out as compared to the corresponding nucleotide of tRNALeu, mechanism for prevention of misediting, overview
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Pyrococcus horikoshii ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: two functions of the enzyme in splicing and aminoacylation in vivo, overview
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
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Substrates: possibly the yeast mitochondria have evolved to tolerate lower levels of fidelity in protein synthesis or have developed alternate mechanisms to enhance discrimination of leucine from non-cognate amino acids that can be misactivated by leucyl-tRNA synthetase
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
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Substrates: LeuRS has a hydrolytic active site that resides in a discrete amino acid editing domain called CP1, LeuRS misactivates many non-leucine amino acids, including isoleucine, valine, methionine, and also structurally similar metabolic cellular intermediate, but the enzyme has an editing active site that is competent for post-transfer editing of mischarged tRNA
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
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Substrates: a two step reaction, the first of which is reversible, aminoacylation and editing by LeuRS require migration of the tRNA acceptor stem end between the canonical aminoacylation core and a separate domain called CP1 that is responsible for amino acid editing, post-transfer editing mechanism., overview
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: the editing active site hydrolytically cleaves the misactivated aminoacyl-adenylate, called pre-transfer editing, or the mischarged tRNA, called post-transfer editing
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
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Substrates: acceptor activity with Tritrichomonas augusta tRNA is 8-fold higher than with yeast tRNA and 25-fold higher than with E. coli tRNA
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
[Mycoplasma] mobile ATCC 43663 / 163K / NCTC 11711
Substrates: -
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ATP + L-leucine + tRNALeu(GAG)
AMP + diphosphate + L-leucyl-tRNALeu(GAG)
-
Substrates: -
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ATP + L-leucine + tRNALeu(GAG)
AMP + diphosphate + L-leucyl-tRNALeu(GAG)
-
Substrates: -
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ATP + L-leucine + tRNALeuCUN
AMP + diphosphate + L-leucyl-tRNALeuCUN
-
Substrates: -
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ATP + L-leucine + tRNALeuCUN
AMP + diphosphate + L-leucyl-tRNALeuCUN
-
Substrates: -
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ATP + L-leucine + tRNALeuUUR
AMP + diphosphate + L-leucyl-tRNALeuUUR
-
Substrates: -
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ATP + L-leucine + tRNALeuUUR
AMP + diphosphate + L-leucyl-tRNALeuUUR
-
Substrates: -
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ATP + L-leucine + tRNAUAALeu
AMP + diphosphate + L-leucyl-tRNACAALeu
Substrates: Mycoplasma mobile tRNAUAALeu (MmtRNAUAALeu) and mutat derivatives
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ATP + L-leucine + tRNAUAALeu
AMP + diphosphate + L-leucyl-tRNACAALeu
[Mycoplasma] mobile ATCC 43663 / 163K / NCTC 11711
Substrates: Mycoplasma mobile tRNAUAALeu (MmtRNAUAALeu) and mutat derivatives
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ATP + L-methionine + tRNALeu
AMP + diphosphate + L-methionyl-tRNALeu
-
Substrates: -
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ATP + L-methionine + tRNALeu
AMP + diphosphate + L-methionyl-tRNALeu
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Substrates: mutant D345A, not the wild-type enzyme
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ATP + L-methionine + tRNALeu
AMP + diphosphate + L-methionyl-tRNALeu
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Substrates: wild-type and CP1 domain mutant enzyme, the mischarged product can be edited by the wild-type enzyme, but not by a recombinant isolated CP1 domain
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ATP + L-methionine + tRNALeu
AMP + diphosphate + L-methionyl-tRNALeu
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Substrates: mutant D419A, not the wild-type enzyme
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ATP + L-norvaline + tRNALeu
AMP + diphosphate + L-norvalyl-tRNALeu
-
Substrates: -
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ATP + L-norvaline + tRNALeu
AMP + diphosphate + L-norvalyl-tRNALeu
-
Substrates: aminoacylation by mutant T252Y
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ATP + L-norvaline + tRNALeu
AMP + diphosphate + L-norvalyl-tRNALeu
Substrates: -
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tubercidin 5'-triphosphate + L-leucine + tRNALeu
tubercidin 5'-phosphate + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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tubercidin 5'-triphosphate + L-leucine + tRNALeu
tubercidin 5'-phosphate + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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tubercidin 5'-triphosphate + L-leucine + tRNALeu
tubercidin 5'-phosphate + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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additional information
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Substrates: the enzyme also performs the ATP-diphosphate exchange reaction
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additional information
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Substrates: the enzymes forms also perform the reversible ATP-diphosphate exchange reaction, which corresponds to the first reaction step
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additional information
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Substrates: isolated editing domain of leucyl-tRNA synthetase from the deep-rooted bacterium Aquifex aeolicus catalyzes the hydrolytic editing of both mischarged tRNALeu and minihelixLeu
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additional information
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-
-
Substrates: aminoacylation of minihelices is strongly dependent on the presence of the A73 identity nucleotide and greatly stimulated by destabilization of the first base pair. Addition of RNA helices that mimic the anticodon domain stimulates minihelixLeu charging by alphabeta-LeuRS indicating possible domain-domain communication. MinihelixLeu cannot be misaminoacylated, perhaps because of the tRNA-independent pretransfer editing activity of alphabeta-LeuRS
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additional information
?
-
-
Substrates: aminoacyl-tRNA is channeled in vivo by probably direct transfer to elongation factor I
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additional information
?
-
-
Substrates: proteolytically derived 34 kDa peptide fragment has lost most of its aminoacylation activity, but retains the ATP-dihosphate exchnage activity, the enzyme also performs the ATP-diphosphate exchange reaction
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?
additional information
?
-
-
Substrates: the enzyme also performs the ATP-diphosphate exchange reaction
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?
additional information
?
-
-
Substrates: the enzyme also performs the ATP-diphosphate exchange reaction, the enzyme has an editing function to correct misaminoacylation of tRNALeu by isoleucine and methionine, T252 is involved
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?
additional information
?
-
-
Substrates: leucine-dependent ATP-diphosphate exchange, leucine + ATP + enzyme/Ile-AMP-enzyme + diphosphate
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?
additional information
?
-
-
Substrates: fidelity of translation is dependent on the specificity of the aminoacyl-tRNA synthetases
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?
additional information
?
-
-
Substrates: Thr247 and Thr248 are two key residues in the Escherichia coli LeuRS editing active site and appear to collaborate in the hydrolytic cleavage mechanism
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?
additional information
?
-
-
Substrates: isolated LeuRS CP1 domain requires idiosyncratic adaptations to confer editing activity independent of the full-length enzyme, overview
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?
additional information
?
-
Substrates: the enzyme has evolved both tRNA-dependent pre- and post-transfer editing capabilities to ensure catalytic specificity
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?
additional information
?
-
Substrates: kinetic origin of substrate specificity in post-transfer editing by leucyl-tRNA synthetase, overview. Binding and catalysis is analyzed independently using cognate leucyl- and non-cognate norvalyl-tRNALeu and their non-hydrolyzable analogues. The amino acid part (leucine versus norvaline) of (mis)aminoacyl-tRNAs can contribute approximately 10fold to ground-state discrimination at the editing site, while the rate of deacylation of leucyl- and norvalyl-tRNALeu differs by about 104fold. Critical role for the A76 3'-OH group of the tRNALeu in post-transfer editing. Molecular dynamics simulations reveals that the wild-type enzyme, but not the T252A mutant, enforces leucine to adopt the side-chain conformation that promotes the steric exclusion of a putative catalytic water. Editing can be distiguished from the synthetic site, which relies on ground-state discrimination in amino acid selection
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additional information
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-
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Substrates: kinetic origin of substrate specificity in post-transfer editing by leucyl-tRNA synthetase, overview. Binding and catalysis is analyzed independently using cognate leucyl- and non-cognate norvalyl-tRNALeu and their non-hydrolyzable analogues. The amino acid part (leucine versus norvaline) of (mis)aminoacyl-tRNAs can contribute approximately 10fold to ground-state discrimination at the editing site, while the rate of deacylation of leucyl- and norvalyl-tRNALeu differs by about 104fold. Critical role for the A76 3'-OH group of the tRNALeu in post-transfer editing. Molecular dynamics simulations reveals that the wild-type enzyme, but not the T252A mutant, enforces leucine to adopt the side-chain conformation that promotes the steric exclusion of a putative catalytic water. Editing can be distiguished from the synthetic site, which relies on ground-state discrimination in amino acid selection
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additional information
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-
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Substrates: residues Y515 and Y520 outside the editing active site of CP1 domain of Giardia lamblia LeuRS are crucial for post-transfer editing by influencing the binding affinity with mischarged tRNALeu
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additional information
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-
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Substrates: measurement of ATP-PPi exchange activity by wild-type and mutant enzymes
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additional information
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-
-
Substrates: substrate specificty with diverse class II tRNALeu isoacceptors and mutants, overview, no activity with tRNALeuG73 and C73, no activity with tRNALeu, tRNASer and tRNATyr from Escherichia coli and Saccharomyces cerevisiae, differences in the tertiary structure of tRNALeu and tRNASer play a key role for inactivity and therefore elimination of native tRNASer as leucine acceptor
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additional information
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Substrates: activity with mitochondrial tRNA mutants associated with some human mitochondrion-related neuromuscular disorders
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additional information
?
-
Substrates: enzyme also performs the ATP-diphosphate exchange reaction
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additional information
?
-
-
Substrates: enzyme also performs the ATP-diphosphate exchange reaction
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additional information
?
-
-
Substrates: LeuRS misactivates several non-cognate amino acids, e.g. Ile and Met as well as the non-standard amino acids norvaline and alpha-amino butyrate. It uses mainly pre-transfer editing to edit alpha-amino butyrate and a tRNA-dependent mechanism to edit norvaline, although both amino acids can be charged to tRNALeu, overview. Separation of the norvaline-editing pathways
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?
additional information
?
-
-
Substrates: the enzyme maintains weak pre-transfer editing activities
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additional information
?
-
-
Substrates: leucine-dependent ATP-diphosphate exchange, leucine + ATP + enzyme/Ile-AMP-enzyme + diphosphate
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?
additional information
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-
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Substrates: leucine-dependent ATP-diphosphate exchange, leucine + ATP + enzyme/Ile-AMP-enzyme + diphosphate
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?
additional information
?
-
-
Substrates: wild-type, full-length enzyme deacylates the pre-formed Ile-tRNALeu
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additional information
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-
-
Substrates: measurement of ATP-PPi exchange activity by wild-type and mutant enzymes
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additional information
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-
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Substrates: no substrates: dATP, GTP, dGTP
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additional information
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-
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Substrates: the LeuRS CP1 domain can also support group I intron RNA splicing in the yeast mitochondria, overview, the RDW peptide, a highly conserved peptide within an RDW-containing motif, is important for enzyme interactions, the RDW peptide is dynamic and forms unique sets of interactions with the aminoacylation and editing complexes, overview
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additional information
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-
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Substrates: leucine-dependent ATP-diphosphate exchange, leucine + ATP + enzyme/Ile-AMP-enzyme + diphosphate
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additional information
?
-
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Substrates: the enzyme maintains weak pretransfer editing activities
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + 2-butynylalanine + tRNALeu
AMP + diphosphate + 2-butynylalanyl-tRNALeu
-
Substrates: aminoacylation by mutant T252Y
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ATP + allylglycine + tRNALeu
AMP + diphosphate + allylglycyl-tRNALeu
-
Substrates: aminoacylation by mutant T252Y
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?
ATP + homoallylglycine + tRNALeu
AMP + diphosphate + homoallylglycyl-tRNALeu
-
Substrates: aminoacylation by mutant T252Y
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?
ATP + homopropargylglycine + tRNALeu
AMP + diphosphate + homopropargylglycyl-tRNALeu
-
Substrates: aminoacylation by mutant T252Y
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?
ATP + L-leucine + tRNAIle
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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?
ATP + L-norisoleucine + tRNALeu
AMP + diphosphate + L-norisoleucyl-tRNALeu
-
Substrates: aminoacylation by mutant T252Y
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?
ATP + L-norvaline + tRNALeu
AMP + diphosphate + L-norvalyl-tRNALeu
-
Substrates: aminoacylation by mutant T252Y
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?
ATP + L-leucine + tRNALeu
?
-
Substrates: esterifies L-leucine to the cognate tRNA in the initial step of protein biosynthesis
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ATP + L-leucine + tRNALeu
?
-
Substrates: mitochondrial enzyme is involved in protein synthesis and mRNA splicing
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: the reaction catalyzed by the enzyme plays an important role in the transport of aminoacylated tRNAs from the nucleus to the cytoplasm
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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r
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: two functions of the enzyme in splicing and aminoacylation in vivo, overview
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: human cytosolic leucyl-tRNA synthetase is one component of a macromolecular aminoacyl-tRNA synthetase complex. The C-terminal peptide of hcLeuRS is critical for the interaction with hcArgRS and the interaction in the multi-tRNA synthetase complex
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: a complex between prolyl-tRNA synthetase, ProRS, and LeuRS in Methanothermobacter thermautotrophicus enhances tRNAPro aminoacylation, overview
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Pyrococcus horikoshii ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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r
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: two functions of the enzyme in splicing and aminoacylation in vivo, overview
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: possibly the yeast mitochondria have evolved to tolerate lower levels of fidelity in protein synthesis or have developed alternate mechanisms to enhance discrimination of leucine from non-cognate amino acids that can be misactivated by leucyl-tRNA synthetase
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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r
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
-
Substrates: -
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?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
Substrates: -
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?
ATP + L-leucine + tRNALeu
AMP + diphosphate + L-leucyl-tRNALeu
[Mycoplasma] mobile ATCC 43663 / 163K / NCTC 11711
Substrates: -
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additional information
?
-
-
Substrates: aminoacyl-tRNA is channeled in vivo by probably direct transfer to elongation factor I
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additional information
?
-
-
Substrates: fidelity of translation is dependent on the specificity of the aminoacyl-tRNA synthetases
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additional information
?
-
Substrates: the enzyme has evolved both tRNA-dependent pre- and post-transfer editing capabilities to ensure catalytic specificity
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additional information
?
-
-
Substrates: LeuRS misactivates several non-cognate amino acids, e.g. Ile and Met as well as the non-standard amino acids norvaline and alpha-amino butyrate. It uses mainly pre-transfer editing to edit alpha-amino butyrate and a tRNA-dependent mechanism to edit norvaline, although both amino acids can be charged to tRNALeu, overview. Separation of the norvaline-editing pathways
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATP
-
optimal concentration for the wild-type enzyme is 4 mM, for the mutants 2 mM
ATP
-
optimal concentration is 4 mM for the wild-type and mutant A293R, for the mutants A293Y, A293G, and A293I it is 2 mM, for the mutants A293D, and As93F it is 1 mM
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ba2+
-
Mg2+, Mn2+, Ca2+ and Ba2+ similarly effective, optimal concentration: 0.1 mM
Ca2+
Co2+
K+
Mg2+
Mn2+
Zn2+
Ca2+
-
can partially replace Mg2+ in activation (in chloroplastic enzyme, not in cytoplasmic enzyme)
Ca2+
-
Mg2+, Mn2+, Ca2+ and Ba2+ similarly effective, optimal concentration: 0.1 mM
Co2+
-
can partially replace Mg2+ in activation (in chloroplastic enzyme, not in cytoplasmic enzyme
K+
-
30 mM KCl enhance activity of cytoplasmic enzyme, no effect on chloroplastic enzyme, concentrations higher than 30 mM inhibit cytoplasmic enzyme more strongly than chloroplastic enzyme
K+
-
the enzyme activity requires high KCl concentration with highest activity in the presence of 3.75 M KCl
K+
-
slight stimulation by 50 mM KCl, progressive inhibition with higher concentrations
Mg2+
-
Mg2+, Mn2+, Ca2+ and Ba2+ similarly effective, optimal concentration: 0.1 mM
Mg2+
-
optimal concentration: 2.5 mM (mitochondrial enzyme), 10 mM (cytoplasmic enzyme)
Mn2+
-
can partially replace Mg2+ in activation (in chloroplastic enzyme, not in cytoplasmic enzyme)
Mn2+
-
Mg2+, Mn2+, Ca2+ and Ba2+ similarly effective, optimal concentration: 0.1 mM
Zn2+
required, zinc is the molecular switch that controls the catalytic cycle of bacterial leucyl-tRNA synthetase. A specialized zinc-binding domain 1 (ZN-1), when associated with Zn2+, assumes a rigid architecture that is stabilized by thiol groups from the residues C159, C176, and C179. When LeuRS is in the aminoacylation complex, these cysteine residues forman equilateral planar triangular configuration with Zn2+, but when LeuRS transitions to the editing conformation, this geometric configuration breaks down. The wild-type enzyme binds Zn2+ to a greater extent than any of the mutant LeuRSs
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-(4-(trifluoromethoxy)phenyl)-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-(4-hydroxybutyl)-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-(4-pentylphenyl)-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-(pyridin-3-yl)-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-octyl-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-phenethyl-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-phenyl-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
((2R,3S,4S,5R)-5-(3-(4-((3-benzylureido)methyl)-1H-1,2,3-triazol-1-yl)propyl)-3,4-dihydroxytetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
((2R,3S,4S,5R)-5-(3-(4-((benzylamino)methyl)-1H-1,2,3-triazol-1-yl)propyl)-3,4-dihydroxytetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
((2R,3S,4S,5R)-5-(3-(4-(aminomethyl)-1H-1,2,3-triazol-1-yl)propyl)-3,4-dihydroxytetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
((2R,3S,4S,5R)-5-(3-(4-(benzamidomethyl)-1H-1,2,3-triazol-1-yl)propyl)-3,4-dihydroxytetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
(2E)-3-(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)-1-phenylprop-2-en-1-one
-
-
(2E)-3-(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-7-yl)-1-phenylprop-2-en-1-one
-
-
(2S)-2-amino-N-(benzenesulfonyl)-4-methylpentanamide
-
MIC against Escherichia coli ATCC 25922 is 0.008 mg/ml
(2S)-2-amino-N-[3-(2-aminopyridin-4-yl)benzene-1-sulfonyl]-4-methylpentanamide
-
-
(2S)-2-amino-N-[3-(6-aminopyridin-2-yl)benzene-1-sulfonyl]-4-methylpentanamide
-
-
(E)-[3-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-7-yl)]acrylic acid ethyl ester
-
-
1-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]-4-methylpentan-2-one
-
-
2'-deoxy-5'-O-[[(2R,3S)-2,3-dihydroxy-4-methylbutanoyl]sulfamoyl]adenosine
-
leucyladenylate sulfamate analogue, targets LRS-mediated mTORC1 inhibition. Compound is effective against cancer cells at low micromolar IC50 concentrations without significant cytotoxicity toward normal cells
2'-deoxy-5'-O-[[(2R,3S)-3-cyclopropyl-2,3-dihydroxypropanoyl]sulfamoyl]-2-iodoadenosine
-
leucyladenylate sulfamate analogue, targets LRS-mediated mTORC1 inhibition. Compound is effective against cancer cells at low micromolar IC50 concentrations without significant cytotoxicity toward normal cells
2'-deoxy-5'-O-[[(2S)-2,4,4-trihydroxybutanoyl]sulfamoyl]adenosine
-
leucyladenylate sulfamate analogue, targets LRS-mediated mTORC1 inhibition. Compound is effective against cancer cells at low micromolar IC50 concentrations without significant cytotoxicity toward normal cells
2-(2,5-dimethylanilino)-5,6,7,8-tetrahydroquinazolin-4(3H)-one
residual activity compared to wild-type enzyme is 71%
2-(2-chlorophenoxy)-N-((3-((L-leucyl)amino)sulfonyl)phenyl)acetamide
-
-
-
2-(2-hydroxy-5-methylanilino)-3,5,6,7-tetrahydro-4H-cyclopenta[d]pyrimidin-4-one
residual activity compared to wild-type enzyme is 40%
2-(2-hydroxy-5-methylanilino)-6-propylpyrimidin-4(3H)-one
residual activity compared to wild-type enzyme is 93%
2-(2-hydroxy-5-methylanilino)quinazolin-4(3H)-one
residual activity compared to wild-type enzyme is 26%
2-(2-hydroxyanilino)-6-methylpyrimidin-4(3H)-one
residual activity compared to wild-type enzyme is 42%
2-(2-hydroxyanilino)pyrimidin-4(3H)-one
residual activity compared to wild-type enzyme is 37%
2-(2-hydroxyanilino)quinazolin-4(3H)-one
residual activity compared to wild-type enzyme is 36%
2-(3-hydroxy-4-methylanilino)-6-propylpyrimidin-4(3H)-one
residual activity compared to wild-type enzyme is 36%
2-(3-hydroxyanilino)-6-methylpyrimidin-4(3H)-one
residual activity compared to wild-type enzyme is 39%
2-(3-hydroxyanilino)quinazolin-4(3H)-one
residual activity compared to wild-type enzyme is 26%
2-(3-methoxyphenoxy)-N-((3-((L-leucyl)amino)sulfonyl)phenyl)acetamide
-
-
-
2-(4-hydroxy-2-methylanilino)-5,6,7,8-tetrahydroquinazolin-4(3H)-one
residual activity compared to wild-type enzyme is 70%
2-(4-hydroxy-2-methylanilino)-6-(propan-2-yl)pyrimidin-4(3H)-one
residual activity compared to wild-type enzyme is 29%
2-(4-hydroxy-2-methylanilino)-6-methylpyrimidin-4(3H)-one
residual activity compared to wild-type enzyme is 61%
2-(4-hydroxy-2-methylanilino)-6-phenylpyrimidin-4(3H)-one
residual activity compared to wild-type enzyme is 94%
2-(4-hydroxyanilino)-6-methylpyrimidin-4(3H)-one
residual activity compared to wild-type enzyme is 28%
2-(4-methoxyphenoxy)-N-((3-((L-leucyl)amino)sulfonyl)phenyl)acetamide
-
-
-
2-(5-chloro-2-hydroxyanilino)-6-propylpyrimidin-4(3H)-one
residual activity compared to wild-type enzyme is 86%
2-([1,1'-biphenyl]-3-yloxy)-N-((3-((L-leucyl)amino)sulfonyl)phenyl)acetamide
-
-
-
2-([1,1'-biphenyl]-4-yloxy)-N-((3-((L-leucyl)amino)sulfonyl)phenyl)acetamide
-
-
-
2-oxo-N-(2-oxo-2H-naphtho[2,1-d][1,3]oxathiol-5-yl)-1,2-dihydrobenzo[cd]indole-6-sulfonamide
inhibits bacterial growth in a bacteriostatic manner
2-[3-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]propyl]-1H-isoindole-1,3(2H)-dione
-
-
3-(2-hydroxy-5-methylanilino)-1,2,4-triazin-5(4H)-one
residual activity compared to wild-type enzyme is 70%
3-(2-hydroxy-5-methylanilino)-6-methyl-1,2,4-triazin-5(4H)-one
residual activity compared to wild-type enzyme is 44%
3-(2-hydroxy-5-methylanilino)-6-phenyl-1,2,4-triazin-5(4H)-one
residual activity compared to wild-type enzyme is 36%
3-(2-hydroxyanilino)-6-methyl-1,2,4-triazin-5(4H)-one
residual activity compared to wild-type enzyme is 38%
3-(3-hydroxy-4-methylanilino)-6-methyl-1,2,4-triazin-5(4H)-one
residual activity compared to wild-type enzyme is 83%
3-(3-hydroxyanilino)-6-methyl-1,2,4-triazin-5(4H)-one
residual activity compared to wild-type enzyme is 40%
3-(3-hydroxyanilino)-6-phenyl-1,2,4-triazin-5(4H)-one
residual activity compared to wild-type enzyme is 57%
3-(4-hydroxy-2-methylanilino)-1,2,4-triazin-5(4H)-one
residual activity compared to wild-type enzyme is 51%
3-(4-hydroxy-2-methylanilino)-6-methyl-1,2,4-triazin-5(4H)-one
residual activity compared to wild-type enzyme is 70%
3-(4-hydroxyanilino)-6-methyl-1,2,4-triazin-5(4H)-one
residual activity compared to wild-type enzyme is 55%
3-(4-hydroxyanilino)-6-phenyl-1,2,4-triazin-5(4H)-one
residual activity compared to wild-type enzyme is 36%
3-(5-chloro-2-hydroxyanilino)-1,2,4-triazin-5(4H)-one
residual activity compared to wild-type enzyme is 45%
3-(5-chloro-2-hydroxyanilino)-6-methyl-1,2,4-triazin-5(4H)-one
residual activity compared to wild-type enzyme is 42%
3-(aminomethyl)-4-chloro-7-ethoxy-2,1-benzoxaborol-1(3H)-ol
i.e. AN6426, an anti-cryptosporidium benzoxaborole
3-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]-3-methylbutan-2-one
-
-
3-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]-4-methylpentan-2-one
-
-
3-[(3-oxo-2,3-dihydro-1,2,4-triazin-5-yl)amino]benzoic acid
residual activity compared to wild-type enzyme is 69%
3-[(4-oxo-3,4-dihydroquinazolin-2-yl)amino]benzoic acid
residual activity compared to wild-type enzyme is 36%
3-[(6-methyl-3-oxo-2,3-dihydro-1,2,4-triazin-5-yl)amino]benzoic acid
residual activity compared to wild-type enzyme is 57%
3-[4-(2-oxopropyl)anilino]-6-phenyl-1,2,4-triazin-5(4H)-one
residual activity compared to wild-type enzyme is 52%
4-(4-bromo-2,3-dimethyl-5-oxo-2,5-dihydro-1H-pyrazol-1-yl)-N-[(pyridin-2-yl)methyl]benzene-1-sulfonamide
-
inhibits the LRS-RagD interaction, shows improved solubility and microsomal stability when compared to BC-LI-0186, shows mTORC1 inhibitory activity of 88.2%
4-(4-chloro-2,3-dimethyl-5-oxo-2,5-dihydro-1H-pyrazol-1-yl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)benzene-1-sulfonamide
-
inhibits the LRS-RagD interaction, shows improved solubility and microsomal stability when compared to BC-LI-0186, shows mTORC1 inhibitory activity of 83.8%
4-(4-isopropyl-2,3-dimethyl-5-oxo-2,5-dihydro-1H-pyrazol-1-yl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)benzene-1-sulfonamide
-
compound inhibits the LRS-RagD interaction, shows mTORC1 inhibitory activity of 78.56%
4-(4-isopropyl-2,3-dimethyl-5-oxo-2,5-dihydro-1H-pyrazol-1-yl)-N-[(pyridin-2-yl)methyl]benzene-1-sulfonamide
-
compound inhibits the LRS-RagD interaction, displays best solubility (193.67 microg/mL in PBS buffer) of the compounds tested
4-amino-N-(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)benzene-1-sulfonamide
-
intracellular activation product of prodrug
4-methyl-3-[(3-oxo-2,3-dihydro-1,2,4-triazin-5-yl)amino]benzoic acid
residual activity compared to wild-type enzyme is 65%
4-methyl-3-[(4-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)amino]benzoic acid
residual activity compared to wild-type enzyme is 56%
4-[(4-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)amino]benzoic acid
residual activity compared to wild-type enzyme is 70%
4-[(5-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)amino]benzoic acid
residual activity compared to wild-type enzyme is 71%
4-[(5-oxo-4,5-dihydro-1,2,4-triazin-3-yl)amino]benzoic acid
residual activity compared to wild-type enzyme is 70%
4-[(6-methyl-3-oxo-2,3-dihydro-1,2,4-triazin-5-yl)amino]benzoic acid
residual activity compared to wild-type enzyme is 64%
5-(2-hydroxy-4-methylanilino)-1,2,4-triazin-3(2H)-one
residual activity compared to wild-type enzyme is 73%
5-(2-hydroxy-5-methylanilino)-1,2,4-triazin-3(2H)-one
residual activity compared to wild-type enzyme is 70%
5-(2-hydroxyanilino)-1,2,4-triazin-3(2H)-one
residual activity compared to wild-type enzyme is 72%
5-(2-hydroxyanilino)-6-methyl-1,2,4-triazin-3(2H)-one
residual activity compared to wild-type enzyme is 67%
5-(4-hydroxy-2-methylanilino)-6-methyl-1,2,4-triazin-3(2H)-one
residual activity compared to wild-type enzyme is 72%
5-(4-hydroxyanilino)-1,2,4-triazin-3(2H)-one
residual activity compared to wild-type enzyme is 70%
5-(4-hydroxyanilino)-6-methyl-1,2,4-triazin-3(2H)-one
residual activity compared to wild-type enzyme is 55%
5-[(6-methyl-3-oxo-2,3-dihydro-1,2,4-triazin-5-yl)amino]benzene-1,3-dicarboxylic acid
residual activity compared to wild-type enzyme is 72%
6,8-dibenzyl-2-(4-methylphenyl)-4,7-dioxo-N-(prop-2-en-1-yl)hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide
-
7-methoxy-1-(5-nitrofuran-2-yl)-1,2,3,4,5,10-hexahydroazepino[3,4-b]indole
compound is bactericidal
8-benzyl-6-[(4-chlorophenyl)methyl]-2-(4-methylphenyl)-4,7-dioxo-N-(prop-2-en-1-yl)hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide
-
8-benzyl-N-([1,1'-biphenyl]-2-yl)-2-methyl-4,7-dioxo-6-(propan-2-yl)hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide
-
9-(5-O-[(2R,3S)-2,3-dihydroxy-4-methylbutanoyl]sulfamoyl-beta-D-arabinofuranosyl)-9H-purin-6-amine
-
leucyladenylate sulfamate analogue, targets LRS-mediated mTORC1 inhibition. Compound is effective against cancer cells at low micromolar IC50 concentrations without significant cytotoxicity toward normal cells
9-(5-O-[(2R,3S)-3-cyclopropyl-2,3-dihydroxypropanoyl]sulfamoyl-beta-D-arabinofuranosyl)-9H-purin-6-amine
-
leucyladenylate sulfamate analogue, targets LRS-mediated mTORC1 inhibition. Compound is effective against cancer cells at low micromolar IC50 concentrations without significant cytotoxicity toward normal cells
Al3+
-
in vitro the enzyme is inhibited by 40% at 0.04 mM, Al3+ inhibits the enzyme in vivo and in vitro, quantitative analysis, in vivo acceptor activity of tRNALeu is decreased by 23% thereby the leucyl-tRNA synthetase activity is increased by 20%, overview
ethyl (2E)-3-(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)prop-2-enoate
-
-
ethyl 2-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]-2-methylpropanoate
-
-
ethyl [(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy](phenyl)acetate
-
-
N,8-dibenzyl-6-[(4-hydroxyphenyl)methyl]-2-methyl-4,7-dioxohexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide
-
N-(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)-4-nitrobenzene-1-sulfonamide
-
i.e. a nitrophenyl sulfonamide-based oxaborole prodrug, compound is converted by bacterial nitroreductases into the amino analogue, which inhibits LeuRS
N-(3-(N-L-leucylsulfamoyl)phenyl)-4-benzyloxybenzamide
-
inhibition of parasite growth with an IC50 of 69.8 microM
N-(4-fluorophenyl)-8-[(furan-2-yl)methyl]-2-methyl-4,7-dioxo-6-[3-[N'-(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)carbamimidamido]propyl]hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide
-
N-benzyl-8-butyl-2-(4-methylphenyl)-4,7-dioxo-6-(propan-2-yl)hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide
-
N-benzyl-8-butyl-6-[(4-chlorophenyl)methyl]-2-(4-methylphenyl)-4,7-dioxohexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide
-
N-benzyl-8-[(furan-2-yl)methyl]-2-(4-methylphenyl)-4,7-dioxo-6-(propan-2-yl)hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide
-
N-tert-butyl-2-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]acetamide
-
-
O-[N-(L-norvalyl)sulfamoyl]adenosine
analogue to the reaction intermediate, non-hydrolyzable
tert-butyl [2-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]ethyl]carbamate
-
-
[4-[(4-oxo-3,4-dihydroquinazolin-2-yl)amino]phenyl]acetic acid
residual activity compared to wild-type enzyme is 37%
[4-[(5-oxo-4,5-dihydro-1,2,4-triazin-3-yl)amino]phenyl]acetic acid
residual activity compared to wild-type enzyme is 72%
[4-[(6-methyl-5-oxo-4,5-dihydro-1,2,4-triazin-3-yl)amino]phenyl]acetic acid
residual activity compared to wild-type enzyme is 71%
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-(4-(trifluoromethoxy)phenyl)-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-(4-(trifluoromethoxy)phenyl)-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-(4-hydroxybutyl)-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-(4-hydroxybutyl)-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-(4-pentylphenyl)-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-(4-pentylphenyl)-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-(pyridin-3-yl)-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-(pyridin-3-yl)-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-octyl-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-octyl-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-phenethyl-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-phenethyl-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-phenyl-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-phenyl-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
((2R,3S,4S,5R)-5-(3-(4-((3-benzylureido)methyl)-1H-1,2,3-triazol-1-yl)propyl)-3,4-dihydroxytetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
((2R,3S,4S,5R)-5-(3-(4-((3-benzylureido)methyl)-1H-1,2,3-triazol-1-yl)propyl)-3,4-dihydroxytetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
((2R,3S,4S,5R)-5-(3-(4-((benzylamino)methyl)-1H-1,2,3-triazol-1-yl)propyl)-3,4-dihydroxytetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
((2R,3S,4S,5R)-5-(3-(4-((benzylamino)methyl)-1H-1,2,3-triazol-1-yl)propyl)-3,4-dihydroxytetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
((2R,3S,4S,5R)-5-(3-(4-(aminomethyl)-1H-1,2,3-triazol-1-yl)propyl)-3,4-dihydroxytetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
((2R,3S,4S,5R)-5-(3-(4-(aminomethyl)-1H-1,2,3-triazol-1-yl)propyl)-3,4-dihydroxytetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
((2R,3S,4S,5R)-5-(3-(4-(benzamidomethyl)-1H-1,2,3-triazol-1-yl)propyl)-3,4-dihydroxytetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
((2R,3S,4S,5R)-5-(3-(4-(benzamidomethyl)-1H-1,2,3-triazol-1-yl)propyl)-3,4-dihydroxytetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
-
2-deoxy-4,5-dihydroxy-1-[5-phenyltetrazole]-D-allo-heptitol-7-N-(leucyl)-sulfamate
-
-
-
2-deoxy-4,5-dihydroxy-1-[5-phenyltetrazole]-D-allo-heptitol-7-N-(leucyl)-sulfamate
-
-
-
5-(5-chloro-2-hydroxy-phenylamino)-2H-[1,2,4]triazin-3-one
binding mode, overview
5-(5-chloro-2-hydroxy-phenylamino)-2H-[1,2,4]triazin-3-one
residual activity compared to wild-type enzyme is 18%, binding mode, overview
5-(5-chloro-2-hydroxy-phenylamino)-6-methyl-2H-[1,2,4]triazin-3-one
binding mode, overview
5-(5-chloro-2-hydroxy-phenylamino)-6-methyl-2H-[1,2,4]triazin-3-one
residual activity compared to wild-type enzyme is 2.3%, binding mode, overview
5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole
-
i.e. AN2690, 0.1 mM, 5fold decrease in aminoacylation activity
5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole
-
i.e. AN2690, the editing active site is the proven target for the broad-spectrum drug. But the post-transfer editing by LeuRS is resistant to the broad-spectrum drug AN2690, AN2690 resistance and its possible mechanism, overview
5-fluoro-2,1-benzoxaborol-1(3H)-ol
-
AN-2690, antibiotic which specifically targets the editing active site of LeuRS
5-fluoro-2,1-benzoxaborol-1(3H)-ol
AN-2690, antibiotic which specifically targets the editing active site of LeuRS
ATP
-
at high concentration, the mutants are more sensisitve than the wild-type enzyme
BC-LI-0186
-
the interaction between RagD and LRS is disrupted by compound BC-LI-0186 inhibitong the translocation of the enzyme to the lysosome
BC-LI-0186
-
compound inhibits the LRS-RagD interaction, exhibits poor solubility and is metabolized by human liver microsomes
additional information
-
aminoacylation and editing reaction are resistant to inactivation by compound AN2690
-
additional information
-
development of a GlLeuRS-specific inhibitor for the treatment of giardiasis
-
additional information
inhibition by high levels of mono- and divalent cations
-
additional information
-
inhibition by high levels of mono- and divalent cations
-
additional information
design and synthesis of tetra-substituted hexahydro-4H-pyrazino[2,1-c][1,2,4]triazine-4,7(6H)-diones as beta-turn mimetics via tandem N-acyliminium cyclization using a parallel synthetic strategy involving both solid and solution-phase reactions. Construction of a 162-member library of tetra-substituted pyrazinotriazinediones with an average purity of 90% using a solid-phase parallel synthesis platform, and screening for the LRS-RagD interaction inhibition by the compounds, overview
-
additional information
derivatives of 5-phenylamino-2H-[1,2,4]triazin-3-one as leucyl-tRNA synthetase (LeuRS) inhibitors, docking study, overview. The inhibitory activity of some compounds against pathogenic LeuRS is 10fold higher compared to the human enzyme. Hydrogen bond-foming amino acids in active site of LeuRS are Phe97, Tyr99, Glu103, His109, Tyr113, Asp137, Ser631, Gly678, Glu680, His681, Gln714, Ile717, Lys759, and Ile760
-
additional information
-
derivatives of 5-phenylamino-2H-[1,2,4]triazin-3-one as leucyl-tRNA synthetase (LeuRS) inhibitors, docking study, overview. The inhibitory activity of some compounds against pathogenic LeuRS is 10fold higher compared to the human enzyme. Hydrogen bond-foming amino acids in active site of LeuRS are Phe97, Tyr99, Glu103, His109, Tyr113, Asp137, Ser631, Gly678, Glu680, His681, Gln714, Ile717, Lys759, and Ile760
-
additional information
not inhibitory: ZCL039, an anti-pneumococcal benzoxaborole inhibiting Streptococcus pneumoniae LRS
-
additional information
derivatives of 5-phenylamino-2H-[1,2,4]triazin-3-one as leucyl-tRNA synthetase (LeuRS) inhibitors, docking study, overview. The inhibitory activity of some compounds against pathogenic LeuRS is 10fold higher compared to the human enzyme. Hydrogen bond-foming amino acids in active site of LeuRS are Phe97, Tyr99, Glu103, His109, Tyr113, Asp137, Ser631, Gly678, Glu680, His681, Gln714, Ile717, Lys759, and Ile760. No inhibition by 5-[(6-methyl-5-oxo-4,5-dihydro-1,2,4-triazin-3-yl)amino]cyclohexa-2,4-diene-1-carboxylic acid, 4-[(4-oxo-3,4,5,6,7,8-hexahydroquinazolin-2-yl)amino]benzoic acid, 2-(2-hydroxyanilino)-5,6,7,8-tetrahydroquinazolin-4(3H)-one, 4-[(6-oxo-4-propyl-1,6-dihydropyrimidin-2-yl)amino]benzoic acid, 2-(4-hydroxyanilino)-6-propylpyrimidin-4(3H)-one, 2-(2-hydroxyanilino)-6-propylpyrimidin-4(3H)-one, 2-(4-hydroxy-2-methylanilino)-6-propylpyrimidin-4(3H)-one, 2-(3-hydroxy-4-methylanilino)-6-propylpyrimidin-4(3H)-one, 3-(2-hydroxyanilino)-1,2,4-triazin-5(4H)-one, 3-(4-hydroxyanilino)-1,2,4-triazin-5(4H)-one, and 2-(2-hydroxyanilino)-3,5,6,7-tetrahydro-4H-cyclopenta[d]pyrimidin-4-one
-
additional information
-
derivatives of 5-phenylamino-2H-[1,2,4]triazin-3-one as leucyl-tRNA synthetase (LeuRS) inhibitors, docking study, overview. The inhibitory activity of some compounds against pathogenic LeuRS is 10fold higher compared to the human enzyme. Hydrogen bond-foming amino acids in active site of LeuRS are Phe97, Tyr99, Glu103, His109, Tyr113, Asp137, Ser631, Gly678, Glu680, His681, Gln714, Ile717, Lys759, and Ile760. No inhibition by 5-[(6-methyl-5-oxo-4,5-dihydro-1,2,4-triazin-3-yl)amino]cyclohexa-2,4-diene-1-carboxylic acid, 4-[(4-oxo-3,4,5,6,7,8-hexahydroquinazolin-2-yl)amino]benzoic acid, 2-(2-hydroxyanilino)-5,6,7,8-tetrahydroquinazolin-4(3H)-one, 4-[(6-oxo-4-propyl-1,6-dihydropyrimidin-2-yl)amino]benzoic acid, 2-(4-hydroxyanilino)-6-propylpyrimidin-4(3H)-one, 2-(2-hydroxyanilino)-6-propylpyrimidin-4(3H)-one, 2-(4-hydroxy-2-methylanilino)-6-propylpyrimidin-4(3H)-one, 2-(3-hydroxy-4-methylanilino)-6-propylpyrimidin-4(3H)-one, 3-(2-hydroxyanilino)-1,2,4-triazin-5(4H)-one, 3-(4-hydroxyanilino)-1,2,4-triazin-5(4H)-one, and 2-(2-hydroxyanilino)-3,5,6,7-tetrahydro-4H-cyclopenta[d]pyrimidin-4-one
-
additional information
-
enzyme drug inhibitor design and development based on the benzoxaborole structure, inhibitory potencies and effectiveness a anti-trypanosomal drugs, ligand, i.e. benzoxaborole-AMP, docking in the LeuRS homology model, overview
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Al3+
-
in vivo acceptor activity of tRNALeu is decreased by 23% thereby the leucyl-tRNA synthetase activity is increased by 20%, overview
additional information
-
a complex between prolyl-tRNA synthetase, ProRS, and LeuRS in Methanothermobacter thermautotrophicus enhances tRNAPro aminoacylation, overview
-
spermidine
-
in absence of Mg2+ spermine allows a very low level of cytoplasmic enzyme
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Acidosis, Lactic
Correction for Li and Guan, "Human Mitochondrial Leucyl-tRNA Synthetase Corrects Mitochondrial Dysfunctions Due to the tRNA(Leu(UUR)) A3243G Mutation, Associated with Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Symptoms and Diabetes".
Acidosis, Lactic
Human mitochondrial leucyl-tRNA synthetase corrects mitochondrial dysfunctions due to the tRNALeu(UUR) A3243G mutation, associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms and diabetes.
Acidosis, Lactic
LARS2 Variants Associated with Hydrops, Lactic Acidosis, Sideroblastic Anemia, and Multisystem Failure.
Acidosis, Lactic
The expanding LARS2 phenotypic spectrum: HLASA, Perrault syndrome with leukodystrophy, and mitochondrial myopathy.
Anemia
Severe course with lethal hepatocellular injury and skeletal muscular dysgenesis in a neonate with infantile liver failure syndrome type 1 caused by novel LARS1 mutations.
Anemia, Sideroblastic
LARS2 Variants Associated with Hydrops, Lactic Acidosis, Sideroblastic Anemia, and Multisystem Failure.
Anemia, Sideroblastic
The expanding LARS2 phenotypic spectrum: HLASA, Perrault syndrome with leukodystrophy, and mitochondrial myopathy.
Carcinogenesis
Implication of leucyl-tRNA synthetase 1 (LARS1) over-expression in growth and migration of lung cancer cells detected by siRNA targeted knock-down analysis.
Carcinogenesis
Inactivation of LARS2, located at the commonly deleted region 3p21.3, by both epigenetic and genetic mechanisms in nasopharyngeal carcinoma.
Carcinoma, Non-Small-Cell Lung
Therapeutic effects of the novel Leucyl-tRNA synthetase inhibitor BC-LI-0186 in non-small cell lung cancer.
CHARGE Syndrome
Laser-capture micro dissection combined with next-generation sequencing analysis of cell type-specific deafness gene expression in the mouse cochlea.
Coma
Prognostic value of time-related Glasgow Coma Scale components in severe traumatic brain injury: a prospective evaluation with respect to 1-year survival and functional outcome.
Deafness
Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy.
Deafness
Characterization of a knock-in mouse model of the homozygous p.V37I variant in Gjb2.
Deafness
The expanding LARS2 phenotypic spectrum: HLASA, Perrault syndrome with leukodystrophy, and mitochondrial myopathy.
Diabetes Mellitus, Type 2
Evidence that the mitochondrial leucyl tRNA synthetase (LARS2) gene represents a novel type 2 diabetes susceptibility gene.
Fetal Growth Retardation
Severe course with lethal hepatocellular injury and skeletal muscular dysgenesis in a neonate with infantile liver failure syndrome type 1 caused by novel LARS1 mutations.
Gram-Negative Bacterial Infections
An assessment of the genetic toxicology of novel boron-containing therapeutic agents.
Hearing Loss
LARS2 Variants Associated with Hydrops, Lactic Acidosis, Sideroblastic Anemia, and Multisystem Failure.
Hearing Loss
Laser-capture micro dissection combined with next-generation sequencing analysis of cell type-specific deafness gene expression in the mouse cochlea.
Hearing Loss
Mutations in LARS2, Encoding Mitochondrial Leucyl-tRNA Synthetase, Lead to Premature Ovarian Failure and Hearing Loss in Perrault Syndrome.
Hearing Loss
Novel Mutations in CLPP, LARS2, CDH23, and COL4A5 Identified in Familial Cases of Prelingual Hearing Loss.
Hearing Loss
The expanding LARS2 phenotypic spectrum: HLASA, Perrault syndrome with leukodystrophy, and mitochondrial myopathy.
Hearing Loss, Sensorineural
Marfanoid habitus is a nonspecific feature of Perrault syndrome.
Hypertension
Prevalence and perinatal outcomes of non-communicable diseases in pregnancy in a regional hospital in Haiti: A prospective cohort study.
Infections
Bacterial resistance to leucyl-tRNA synthetase inhibitor GSK2251052 develops during treatment of complicated urinary tract infections.
Infections
Directive clinique no 409 : Tests diagnostiques ftaux intra-utérins en cas d'infection virale chronique maternelle.
Infections
Discovery of a potent benzoxaborole-based anti-pneumococcal agent targeting leucyl-tRNA synthetase.
Infections
Recent development of leucyl-tRNA synthetase inhibitors as antimicrobial agents.
Kallmann Syndrome
Laser-capture micro dissection combined with next-generation sequencing analysis of cell type-specific deafness gene expression in the mouse cochlea.
leucine-trna ligase deficiency
Leucyl-tRNA synthetase deficiency systemically induces excessive autophagy in zebrafish.
Liver Failure
Deep phenotyping of MARS1 (interstitial lung and liver disease) and LARS1 (infantile liver failure syndrome 1) recessive multisystemic disease using Human Phenotype Ontology annotation: Overlap and differences. Case report and review of literature.
Liver Failure
Genotypic diversity and phenotypic spectrum of infantile liver failure syndrome type 1 due to variants in LARS1.
Liver Failure
Infantile Liver Failure Syndrome 1 associated with a novel variant of the LARS1 gene: Clinical, genetic, and functional characterization.
Liver Failure
Severe course with lethal hepatocellular injury and skeletal muscular dysgenesis in a neonate with infantile liver failure syndrome type 1 caused by novel LARS1 mutations.
Liver Failure
[Clinical feature and molecular diagnostic analysis of the first non-caucasian child with infantile liver failure syndrome type 1].
Liver Failure, Acute
Severe course with lethal hepatocellular injury and skeletal muscular dysgenesis in a neonate with infantile liver failure syndrome type 1 caused by novel LARS1 mutations.
Lung Diseases
A Leucyl-tRNA Synthetase Inhibitor with Broad-Spectrum Anti-Mycobacterial Activity.
Lung Neoplasms
Implication of leucyl-tRNA synthetase 1 (LARS1) over-expression in growth and migration of lung cancer cells detected by siRNA targeted knock-down analysis.
Lung Neoplasms
Therapeutic effects of the novel Leucyl-tRNA synthetase inhibitor BC-LI-0186 in non-small cell lung cancer.
Mandibulofacial Dysostosis
Laser-capture micro dissection combined with next-generation sequencing analysis of cell type-specific deafness gene expression in the mouse cochlea.
MELAS Syndrome
Correction of the consequences of mitochondrial 3243A>G mutation in the MT-TL1 gene causing the MELAS syndrome by tRNA import into mitochondria.
MELAS Syndrome
Exploring the Ability of LARS2 Carboxy-Terminal Domain in Rescuing the MELAS Phenotype.
Mitochondrial Diseases
Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy.
Mitochondrial Encephalomyopathies
Correction for Li and Guan, "Human Mitochondrial Leucyl-tRNA Synthetase Corrects Mitochondrial Dysfunctions Due to the tRNA(Leu(UUR)) A3243G Mutation, Associated with Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Symptoms and Diabetes".
Mitochondrial Encephalomyopathies
Human mitochondrial leucyl-tRNA synthetase corrects mitochondrial dysfunctions due to the tRNALeu(UUR) A3243G mutation, associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms and diabetes.
Mitochondrial Myopathies
The expanding LARS2 phenotypic spectrum: HLASA, Perrault syndrome with leukodystrophy, and mitochondrial myopathy.
Muscular Diseases
The expanding LARS2 phenotypic spectrum: HLASA, Perrault syndrome with leukodystrophy, and mitochondrial myopathy.
Nasopharyngeal Carcinoma
Inactivation of LARS2, located at the commonly deleted region 3p21.3, by both epigenetic and genetic mechanisms in nasopharyngeal carcinoma.
Nasopharyngitis
Inactivation of LARS2, located at the commonly deleted region 3p21.3, by both epigenetic and genetic mechanisms in nasopharyngeal carcinoma.
Neoplasms
An In Vivo Gain-of-Function Screen Identifies the Williams-Beuren Syndrome Gene GTF2IRD1 as a Mammary Tumor Promoter.
Neoplasms
Avoir sa santé en main : le sentiment d'habilitation tel que perçu par les jeunes adultes souffrant d'un cancer avancé.
Neoplasms
Concept d'adaptation chez les conjoints de femmes iraniennes atteintes du cancer du sein: étude qualitative basée sur une approche phénoménologique.
Neoplasms
Connaissances, attitudes et croyances concernant le dépistage du cancer du col utérin dans le District d'Ajumako-Enyan-Essiam au Ghana.
Neoplasms
Degrés de collaboration perçus entre les patients atteints de cancer et leurs prestataires de soins pendant la radiothérapie.
Neoplasms
Élaboration d'un énoncé de position national sur la navigation des patients atteints de cancer au Canada.
Neoplasms
Implication of leucyl-tRNA synthetase 1 (LARS1) over-expression in growth and migration of lung cancer cells detected by siRNA targeted knock-down analysis.
Neoplasms
Optimiser les soins des adultes âgés atteints de cancer et l'accompagnement de leurs proches: énoncé de position et contribution des infirmières canadiennes en oncologie.
Neoplasms
Plant tumour biocontrol agent employs a tRNA-dependent mechanism to inhibit leucyl-tRNA synthetase.
Nephritis, Hereditary
Laser-capture micro dissection combined with next-generation sequencing analysis of cell type-specific deafness gene expression in the mouse cochlea.
Neurologic Manifestations
Biallelic mutations in LARS2 can cause Perrault syndrome type 2 with neurologic symptoms.
Onychomycosis
An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site.
Primary Ovarian Insufficiency
Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy.
Primary Ovarian Insufficiency
LARS2 Variants Associated with Hydrops, Lactic Acidosis, Sideroblastic Anemia, and Multisystem Failure.
Primary Ovarian Insufficiency
Marfanoid habitus is a nonspecific feature of Perrault syndrome.
Primary Ovarian Insufficiency
Mutations in LARS2, Encoding Mitochondrial Leucyl-tRNA Synthetase, Lead to Premature Ovarian Failure and Hearing Loss in Perrault Syndrome.
Primary Ovarian Insufficiency
The expanding LARS2 phenotypic spectrum: HLASA, Perrault syndrome with leukodystrophy, and mitochondrial myopathy.
Squamous Cell Carcinoma of Head and Neck
Promoter methylation of cyclin A1 is associated with human papillomavirus 16 induced head and neck squamous cell carcinoma independently of p53 mutation.
Starvation
In vivo regulatory responses of four Escherichia coli operons which encode leucyl-tRNAs.
Starvation
Membrane association of leucyl-tRNA synthetase during leucine starvation in Escherichia coli.
Starvation
Mitochondrial leucine tRNA level and PTCD1 are regulated in response to leucine starvation.
Starvation
Regulation of the nuclear genes encoding the cytoplasmic and mitochondrial leucyl-tRNA synthetases of Neurospora crassa.
Starvation
Yeast proteinase yscB inactivates the leucyl tRNA synthetase in extracts of Saccharomyces cerevisiae.
Stroke
A video-game group intervention: Experiences and perceptions of adults with chronic stroke and their therapists: Intervention de groupe à l'aide de jeux vidéo : Expériences et perceptions d'adultes en phase chronique d'un accident vasculaire cérébral et de leurs ergothérapeutes.
Tuberculosis
A Leucyl-tRNA Synthetase Inhibitor with Broad-Spectrum Anti-Mycobacterial Activity.
Tuberculosis
A prokaryote and human tRNA synthetase provide an essential RNA splicing function in yeast mitochondria.
Tuberculosis
Crucial role of the C-terminal domain of Mycobacterium tuberculosis leucyl-tRNA synthetase in aminoacylation and editing.
Tuberculosis
Discovery of a Potent and Specific M. tuberculosis Leucyl-tRNA Synthetase Inhibitor: (S)-3-(Aminomethyl)-4-chloro-7-(2-hydroxyethoxy)benzo[c][1,2]oxaborol-1(3H)-ol (GSK656).
Tuberculosis
Discovery of novel antituberculosis agents among 3-phenyl-5-(1-phenyl-1H-[1,2,3]triazol-4-yl)-[1,2,4]oxadiazole derivatives targeting aminoacyl-tRNA synthetases.
Tuberculosis
Discovery of novel oral protein synthesis inhibitors of Mycobacterium tuberculosis that target leucyl-tRNA synthetase.
Tuberculosis
Discovery of potent anti-tuberculosis agents targeting leucyl-tRNA synthetase.
Tuberculosis
Dual-target inhibitors of mycobacterial aminoacyl-tRNA synthetases among N-benzylidene-N'-thiazol-2-yl-hydrazines.
Tuberculosis
First-Time-in-Human Study and Prediction of Early Bactericidal Activity for GSK3036656, a Potent Leucyl-tRNA Synthetase Inhibitor for Tuberculosis Treatment.
Tuberculosis
Identification of Mycobacterium tuberculosis leucyl-tRNA synthetase (LeuRS) inhibitors among the derivatives of 5-phenylamino-2H-[1,2,4]triazin-3-one.
Urinary Tract Infections
Bacterial resistance to leucyl-tRNA synthetase inhibitor GSK2251052 develops during treatment of complicated urinary tract infections.
Usher Syndromes
Laser-capture micro dissection combined with next-generation sequencing analysis of cell type-specific deafness gene expression in the mouse cochlea.
Waardenburg Syndrome
Laser-capture micro dissection combined with next-generation sequencing analysis of cell type-specific deafness gene expression in the mouse cochlea.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0076
tRNALeu(UAG)
-
in 100 mM Tris-HCl (pH 7.8), 30 mM KCl, 12 mM MgCl2, 5 mM dithiothreitol, at 30°C
-
0.725
ATP
-
37°C, pH 7.6, leucylation, DELTAChcLeuRS (a C-terminal 89-amino acid truncated enzyme form)
1.349
ATP
-
37°C, pH 7.6, ATP-diphosphate exchange, DELTAChcLeuRS (a C-terminal 89-amino acid truncated enzyme form)
0.002
Ile-tRNALeu
mutant enzyme R185E, in 100 mM HEPES (pH 7.8), 10 mM MgCl2, at 37°C
-
0.0021
Ile-tRNALeu
wild type enzyme, in 100 mM HEPES (pH 7.8), 10 mM MgCl2, at 37°C
-
0.0024
Ile-tRNALeu
mutant enzyme R286E, in 100 mM HEPES (pH 7.8), 10 mM MgCl2, at 37°C
-
0.0025
Ile-tRNALeu
mutant enzyme E184R, in 100 mM HEPES (pH 7.8), 10 mM MgCl2, at 37°C
-
2.8
L-isoleucine
-
ATP-diphosphate exchange reaction, mutant enzyme, pH 7.8, 37°C
3.5
L-isoleucine
-
ATP-diphosphate exchange reaction, wild-type enzyme, pH 7.8, 37°C
0.0058
L-leucine
-
37°C, pH 7.6, leucylation, DELTAChcLeuRS (a C-terminal 89-amino acid truncated enzyme form)
0.00843
L-leucine
-
isoform LeuRS1, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
0.015
L-leucine
-
aminoacylation reaction, wild-type and mutant enzyme, pH 7.8, 37°C
0.039
L-leucine
wild type enzyme, in 100 mM HEPES (pH 7.8), 10 mM MgCl2, at 37°C
0.052
L-leucine
-
ATP-diphosphate exchange reaction, wild-type enzyme, pH 7.8, 37°C
0.064
L-leucine
-
37°C, pH 7.6, ATP-diphosphate exchange, DELTAChcLeuRS (a C-terminal 89-amino acid truncated enzyme form)
0.069
L-leucine
-
ATP-diphosphate exchange reaction, mutant enzyme, pH 7.8, 37°C
0.891
L-leucine
-
isoform LeuRS2, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
0.01251
L-leucyl-Pyrococcus horikoshii tRNALeu(GAG)
-
isoform LeuRS1, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
-
0.01643
L-leucyl-Pyrococcus horikoshii tRNALeu(GAG)
-
isoform LeuRS2, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
-
6.2
L-methionine
-
ATP-diphosphate exchange reaction, mutant enzyme, pH 7.8, 37°C
7.5
L-methionine
-
ATP-diphosphate exchange reaction, wild-type enzyme, pH 7.8, 37°C
0.01101
Natrialba magadii tRNALeu(CAA)
-
isoform LeuRS1, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
-
0.01313
Natrialba magadii tRNALeu(CAA)
-
isoform LeuRS2, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
-
0.00335
Natrialba magadii tRNALeu(GAG)
-
isoform LeuRS2, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
-
0.00773
Natrialba magadii tRNALeu(GAG)
-
isoform LeuRS1, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
-
0.0003
tRNAGAGLeu
pH 7.8, 65°C, recombinant wild-type enzyme
-
0.00081
tRNAGAGLeu
pH 7.8, 65°C, recombinant mutant R94A/R98A
-
0.00088
tRNAGAGLeu
pH 7.8, 65°C, recombinant mutant R94E/R98E
-
0.0014
tRNALeu
-
37°C, pH 7.6, tRNALeu from calf liver, leucylation, DELTAChcLeuRS (a C-terminal 89-amino acid truncated enzyme form)
0.0019
tRNALeu
-
37°C, pH 7.6, tRNALeu from calf liver, leucylation, full-length enzyme
0.0003
tRNALeu from Aquifex aeolicus
-
aminoacylation reaction, pH 7.8, 60°C
-
0.00038
tRNALeu from Aquifex aeolicus
-
aminoacylation reaction, pH 7.8, 37°C
-
0.00076
tRNALeu from Escherichia coli
-
aminoacylation reaction, pH 7.8, 37°C
-
0.0015
tRNALeu from Escherichia coli
-
aminoacylation reaction, pH 7.8, 60°C
-
0.0075
tRNALeu(GAG)
-
in 100 mM Tris-HCl (pH 7.8), 30 mM KCl, 12 mM MgCl2, 5 mM dithiothreitol, at 30°C
-
0.0002
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant wild-type enzyme
-
0.0004
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant wild-type enzyme
-
0.0017
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant mutant L570F
-
0.0018
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant mutants K600L and K600R
-
0.002
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant mutant L570R
-
0.0022
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant mutant K600F
-
0.025
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant mutant L570K
-
0.000018
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant mutant L570K
-
0.00016
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant wild-type enzyme
-
0.0015
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant mutant K600L
-
0.0017
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant mutant L570F
-
0.004
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant wild-type enzyme
-
0.004
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant mutant K600R
-
0.006
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant mutant K600F
-
additional information
additional information
-
kinetics, wild-type and mutant enzymes
-
additional information
additional information
-
kinetics, wild-type and mutant enzymes
-
additional information
additional information
-
substrate specificity with diverse tRNALeu isoacceptors and mutants
-
additional information
additional information
-
turnover numbers for tRNALeu(UUR) variants
-
additional information
additional information
-
KM-values for hydrolytic editing of mischarged Ile-tRNALeu(GAG)
-
additional information
additional information
-
kinetics of recombinant His-tagged wild-type and mutant enzymes
-
additional information
additional information
-
prolyl-tRNA synthetase, ProRS, and LeuRS interaction kinetics
-
additional information
additional information
-
kinetics of recombinant wild-type and mutant enzymes
-
additional information
additional information
-
kinetics of mischarging and post-transfer editing activities, overview
-
additional information
additional information
-
kinetics of recombinant trunacted mutants, overview
-
additional information
additional information
-
kinetics of chimeric mutants
-
additional information
additional information
-
kinetics of wild-type and mutant enzymes, overview
-
additional information
additional information
-
kcat/Km: 1 (ATP, wild-type), 1 (Leu, wild-type), 0.43 (ATP, mutant K587A), 0.42 (Leu, mutant K587A), 0.57 (ATP, mutant K588A), 0.37 (Leu, mutant K588A), 0.91 (ATP, mutant D603A), 0.94 (Leu, mutant D603A), 0.98 (ATP, mutant K606R), 0.99 (Leu, mutant K606R), 0.9 (ATP, mutant K606E), 0.99 (Leu, mutant K606E), 0.85 (ATP, mutant K606L), 0.98 (Leu, mutant K606L), 0.86 (ATP, mutant K606D), 0.83 (Leu, mutant K606D)
-
additional information
additional information
-
steady-state leucine activation and aminoacylation kinetics of GlLeuRS and its mutants, overview
-
additional information
additional information
-
kinetic constants of wild-type and D399A mutant of LeuRS in amino acid activation reaction with different amino acids, overview. Cytoplasmic LeuRS overexpressed in Escherichia coli exhibits the same kcat values as the one overexpressed in insect cells using in vitro transcribed tRNA
-
additional information
additional information
-
equilibrium kinetics of wild-type and mutant enzymes, overview
-
additional information
additional information
determination of dissociation constants of Zn2+ from LeuRS enzymes
-
additional information
additional information
-
determination of dissociation constants of Zn2+ from LeuRS enzymes
-
additional information
additional information
kinetic origin of substrate specificity in post-transfer editing by leucyl-tRNA synthetase, single-turnover measurements, overview
-
additional information
additional information
-
kinetic origin of substrate specificity in post-transfer editing by leucyl-tRNA synthetase, single-turnover measurements, overview
-
additional information
additional information
kinetics of aminoacylation reaction of recombinant wild-type and mutant enzymes, and apparent kinetic parameters for hydrolytic editing of mischarged Met-tRNALeu, overview
-
additional information
additional information
-
kinetics of aminoacylation reaction of recombinant wild-type and mutant enzymes, and apparent kinetic parameters for hydrolytic editing of mischarged Met-tRNALeu, overview
-
additional information
additional information
dissociation constants of LeuRS and mutants from human cytoplasm for their cognate tRNAs
-
additional information
additional information
dissociation constants of LeuRS and mutants from Escherichia coli for their cognate tRNAs. Reaction kinetics of EcLeuRS for Mycoplasma mobile MmtRNAUAALeu and mutant variants, kinetic constants of EcLeuRS, chimeric LeuRS and their mutants for tRNALeu in aminoacylation reaction and for AMP formation in the presence of Nva and MmtRNACAA, detailed overview
-
additional information
additional information
-
dissociation constants of LeuRS and mutants from Escherichia coli for their cognate tRNAs. Reaction kinetics of EcLeuRS for Mycoplasma mobile MmtRNAUAALeu and mutant variants, kinetic constants of EcLeuRS, chimeric LeuRS and their mutants for tRNALeu in aminoacylation reaction and for AMP formation in the presence of Nva and MmtRNACAA, detailed overview
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2
tRNALeu(UAG)
-
in 100 mM Tris-HCl (pH 7.8), 30 mM KCl, 12 mM MgCl2, 5 mM dithiothreitol, at 30°C
-
0.55
ATP
-
37°C, pH 7.6, leucylation, DELTAChcLeuRS (a C-terminal 89-amino acid truncated enzyme form)
0.74
ATP
-
37°C, pH 7.6, ATP-diphosphate exchange, DELTAChcLeuRS (a C-terminal 89-amino acid truncated enzyme form)
7
Ile-tRNALeu
wild type enzyme, in 100 mM HEPES (pH 7.8), 10 mM MgCl2, at 37°C
-
7.4
Ile-tRNALeu
mutant enzyme R286E, in 100 mM HEPES (pH 7.8), 10 mM MgCl2, at 37°C
-
7.6
Ile-tRNALeu
mutant enzyme R185E, in 100 mM HEPES (pH 7.8), 10 mM MgCl2, at 37°C
-
8.8
Ile-tRNALeu
mutant enzyme E184R, in 100 mM HEPES (pH 7.8), 10 mM MgCl2, at 37°C
-
6.9
L-isoleucine
-
ATP-diphosphate exchange reaction, mutant enzyme, pH 7.8, 37°C
18
L-isoleucine
-
ATP-diphosphate exchange reaction, wild-type enzyme, pH 7.8, 37°C
0.00961
L-leucine
-
isoform LeuRS2, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
0.56
L-leucine
-
37°C, pH 7.6, leucylation, DELTAChcLeuRS (a C-terminal 89-amino acid truncated enzyme form)
0.563
L-leucine
-
isoform LeuRS1, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
0.81
L-leucine
-
37°C, pH 7.6, ATP-diphosphate exchange, DELTAChcLeuRS (a C-terminal 89-amino acid truncated enzyme form)
73.7
L-leucine
wild type enzyme, in 100 mM HEPES (pH 7.8), 10 mM MgCl2, at 37°C
101
L-leucine
-
ATP-diphosphate exchange reaction, mutant enzyme, pH 7.8, 37°C
171
L-leucine
-
ATP-diphosphate exchange reaction, wild-type enzyme, pH 7.8, 37°C
0.00119
L-leucyl-Pyrococcus horikoshii tRNALeu(GAG)
-
isoform LeuRS2, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
-
0.0418
L-leucyl-Pyrococcus horikoshii tRNALeu(GAG)
-
isoform LeuRS1, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
-
7.6
L-methionine
-
ATP-diphosphate exchange reaction, mutant enzyme, pH 7.8, 37°C
19
L-methionine
-
ATP-diphosphate exchange reaction, wild-type enzyme, pH 7.8, 37°C
0.000418
Natrialba magadii tRNALeu(CAA)
-
isoform LeuRS2, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
-
0.0464
Natrialba magadii tRNALeu(CAA)
-
isoform LeuRS1, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
-
0.000668
Natrialba magadii tRNALeu(GAG)
-
isoform LeuRS2, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
-
0.064
Natrialba magadii tRNALeu(GAG)
-
isoform LeuRS1, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
-
0.028
tRNALeu
-
37°C, pH 7.6, tRNALeu from calf liver, leucylation, full-length enzyme
0.059
tRNALeu
-
37°C, pH 7.6, tRNALeu from calf liver, leucylation, DELTAChcLeuRS (a C-terminal 89-amino acid truncated enzyme form)
0.39
tRNALeu from Aquifex aeolicus
-
aminoacylation reaction, pH 7.8, 37°C
-
0.084
tRNALeu from Escherichia coli
-
aminoacylation reaction, pH 7.8, 37°C
-
1.8
tRNALeu(GAG)
-
in 100 mM Tris-HCl (pH 7.8), 30 mM KCl, 12 mM MgCl2, 5 mM dithiothreitol, at 30°C
-
0.35
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant mutant K600L
-
0.39
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant wild-type enzyme
-
3
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant mutant K600F
-
3.2
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant mutant K600R
-
9.8
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant mutant L570K
-
14.5
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant wild-type enzyme
-
21
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant mutant L570R
-
24
tRNALeuCUN
-
Escherichia coli derived substrate, pH 7.0, 37°C, recombinant mutant L570F
-
0.000018
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant mutant L570K
-
0.00016
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant wild-type enzyme
-
0.0017
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant mutant L570F
-
0.003
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant mutant K600L
-
0.09
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant wild-type enzyme
-
0.13
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant mutant K600F
-
0.14
tRNALeuUUR
-
human derived substrate, pH 7.0, 37°C, recombinant mutant K600R
-
additional information
additional information
-
turnover numbers for tRNALeu(UUR) variants
-
additional information
additional information
-
turnover number for hydrolytic editing of mischarged Ile-tRNALeu(GAG)
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
240
tRNALeu(GAG)
-
in 100 mM Tris-HCl (pH 7.8), 30 mM KCl, 12 mM MgCl2, 5 mM dithiothreitol, at 30°C
-
260
tRNALeu(UAG)
-
in 100 mM Tris-HCl (pH 7.8), 30 mM KCl, 12 mM MgCl2, 5 mM dithiothreitol, at 30°C
-
3100
Ile-tRNALeu
mutant enzyme R286E, in 100 mM HEPES (pH 7.8), 10 mM MgCl2, at 37°C
-
3300
Ile-tRNALeu
wild type enzyme, in 100 mM HEPES (pH 7.8), 10 mM MgCl2, at 37°C
-
3500
Ile-tRNALeu
mutant enzyme E184R, in 100 mM HEPES (pH 7.8), 10 mM MgCl2, at 37°C
-
3800
Ile-tRNALeu
mutant enzyme R185E, in 100 mM HEPES (pH 7.8), 10 mM MgCl2, at 37°C
-
0.0108
L-leucine
-
isoform LeuRS2, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
66.8
L-leucine
-
isoform LeuRS1, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
1890
L-leucine
wild type enzyme, in 100 mM HEPES (pH 7.8), 10 mM MgCl2, at 37°C
0.0724
L-leucyl-Pyrococcus horikoshii tRNALeu(GAG)
-
isoform LeuRS2, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
-
3.34
L-leucyl-Pyrococcus horikoshii tRNALeu(GAG)
-
isoform LeuRS1, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
-
0.0318
Natrialba magadii tRNALeu(CAA)
-
isoform LeuRS2, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
-
4.21
Natrialba magadii tRNALeu(CAA)
-
isoform LeuRS1, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
-
0.199
Natrialba magadii tRNALeu(GAG)
-
isoform LeuRS2, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
-
9.28
Natrialba magadii tRNALeu(GAG)
-
isoform LeuRS1, in 20 mM Tris-HCl, pH 9.0, 3.5 M KCl, 30 mM MgCl2, 1 mM dithiohtreitol, at 40°C
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000178
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-(4-(trifluoromethoxy)phenyl)-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
pH 7.5, 37°C
0.0003877
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-(4-hydroxybutyl)-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
pH 7.5, 37°C
0.0000055
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-(4-pentylphenyl)-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
pH 7.5, 37°C
0.0000316
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-(pyridin-3-yl)-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
pH 7.5, 37°C
0.0000524
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-octyl-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
pH 7.5, 37°C
0.0001084
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-phenethyl-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
pH 7.5, 37°C
0.0000025
((2R,3S,4S,5R)-3,4-dihydroxy-5-(3-(4-phenyl-1H-1,2,3-triazol-1-yl)propyl)tetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
pH 7.5, 37°C
0.0001824
((2R,3S,4S,5R)-5-(3-(4-((3-benzylureido)methyl)-1H-1,2,3-triazol-1-yl)propyl)-3,4-dihydroxytetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
pH 7.5, 37°C
0.001261
((2R,3S,4S,5R)-5-(3-(4-((benzylamino)methyl)-1H-1,2,3-triazol-1-yl)propyl)-3,4-dihydroxytetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
pH 7.5, 37°C
0.00297
((2R,3S,4S,5R)-5-(3-(4-(aminomethyl)-1H-1,2,3-triazol-1-yl)propyl)-3,4-dihydroxytetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
pH 7.5, 37°C
0.0000313
((2R,3S,4S,5R)-5-(3-(4-(benzamidomethyl)-1H-1,2,3-triazol-1-yl)propyl)-3,4-dihydroxytetrahydro-2H-pyran-2-yl)methyl leucylsulfamate
-
pH 7.5, 37°C
0.000031
2-deoxy-4,5-dihydroxy-1-[5-phenyltetrazole]-D-allo-heptitol-7-N-(leucyl)-sulfamate
-
pH 7.5, 37°C
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.209
(2E)-3-(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)-1-phenylprop-2-en-1-one
Trypanosoma brucei
-
pH 7.8, 37°C
0.412
(2E)-3-(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-7-yl)-1-phenylprop-2-en-1-one
Trypanosoma brucei
-
pH 7.8, 37°C
0.000013
(2S)-2-amino-4-methyl-N-[3-(pyridin-4-yl)benzene-1-sulfonyl]pentanamide
Escherichia coli
-
pH not specified in the publication, temperature not specified in the publication
0.000035
(2S)-2-amino-N-(benzenesulfonyl)-4-methylpentanamide
Escherichia coli
-
pH not specified in the publication, temperature not specified in the publication
0.000032
(2S)-2-amino-N-([1,1'-biphenyl]-3-sulfonyl)-4-methylpentanamide
Escherichia coli
-
pH not specified in the publication, temperature not specified in the publication
0.000014
(2S)-2-amino-N-[3-(2-aminopyridin-4-yl)benzene-1-sulfonyl]-4-methylpentanamide
Escherichia coli
-
pH not specified in the publication, temperature not specified in the publication
0.000023
(2S)-2-amino-N-[3-(6-aminopyridin-2-yl)benzene-1-sulfonyl]-4-methylpentanamide
Escherichia coli
-
pH not specified in the publication, temperature not specified in the publication
1
(E)-[3-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-7-yl)]acrylic acid ethyl ester
Trypanosoma brucei
-
above, pH 7.8, 37°C
0.0323
1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl cyclohexylcarbamate
Trypanosoma brucei
-
pH 7.8, 37°C
0.0431
1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl phenylcarbamate
Trypanosoma brucei
-
pH 7.8, 37°C
0.0676
1-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]-4-methylpentan-2-one
Trypanosoma brucei
-
pH 7.8, 37°C
0.0272
1-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]butan-2-one
Trypanosoma brucei
-
pH 7.8, 37°C
0.0308
1-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]pentan-2-one
Trypanosoma brucei
-
pH 7.8, 37°C
0.0057
2-(2-chlorophenoxy)-N-((3-((L-leucyl)amino)sulfonyl)phenyl)acetamide
Trypanosoma brucei
-
pH 7.8, 37°C
-
0.0027
2-(3-methoxyphenoxy)-N-((3-((L-leucyl)amino)sulfonyl)phenyl)acetamide
Trypanosoma brucei
-
pH 7.8, 37°C
-
0.0036
2-(4-methoxyphenoxy)-N-((3-((L-leucyl)amino)sulfonyl)phenyl)acetamide
Trypanosoma brucei
-
pH 7.8, 37°C
-
0.0068
2-(4-nitrophenoxy)-N-((3-((L-leucyl)amino)sulfonyl)phenyl)acetamide
Trypanosoma brucei
-
pH 7.8, 37°C
-
0.0007
2-([1,1'-biphenyl]-3-yloxy)-N-((3-((L-leucyl)amino)sulfonyl)phenyl)acetamide
Trypanosoma brucei
-
pH 7.8, 37°C
-
0.0073
2-([1,1'-biphenyl]-4-yloxy)-N-((3-((L-leucyl)amino)sulfonyl)phenyl)acetamide
Trypanosoma brucei
-
pH 7.8, 37°C
-
0.023
2-oxo-N-(2-oxo-2H-naphtho[2,1-d][1,3]oxathiol-5-yl)-1,2-dihydrobenzo[cd]indole-6-sulfonamide
Pseudomonas aeruginosa
pH 7.5, 37°C
0.0055
2-phenoxy-N-((3-((L-leucyl)amino)sulfonyl)phenyl)acetamide
Trypanosoma brucei
-
pH 7.8, 37°C
-
0.0025
2-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]pentan-3-one
Trypanosoma brucei
-
pH 7.8, 37°C
0.1
2-[3-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]propyl]-1H-isoindole-1,3(2H)-dione
Trypanosoma brucei
-
above, pH 7.8, 37°C
0.0077
3-(aminomethyl)-4-chloro-7-ethoxy-2,1-benzoxaborol-1(3H)-ol
Homo sapiens
pH 7.5,37°C
0.005
3-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]-3-methylbutan-2-one
Trypanosoma brucei
-
pH 7.8, 37°C
0.0045
3-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]-4-methylpentan-2-one
Trypanosoma brucei
-
pH 7.8, 37°C
0.0038
3-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]butan-2-one
Trypanosoma brucei
-
pH 7.8, 37°C
0.0029
3-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]heptan-4-one
Trypanosoma brucei
-
pH 7.8, 37°C
0.0314
3-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]hexan-2-one
Trypanosoma brucei
-
pH 7.8, 37°C
0.0035
3-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]pentan-2-one
Trypanosoma brucei
-
pH 7.8, 37°C
0.003
4-amino-N-(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)benzene-1-sulfonamide
Staphylococcus aureus
-
pH not specified in the publication, temperature not specified in the publication
0.1
6-(pyridin-2-ylmethoxy)-2,1-benzoxaborol-1(3H)-ol
Trypanosoma brucei
-
above, pH 7.8, 37°C
0.1
6-[(3-hydroxypentan-2-yl)oxy]-2,1-benzoxaborol-1(3H)-ol
Trypanosoma brucei
-
above, pH 7.8, 37°C
0.015
7-methoxy-1-(5-nitrofuran-2-yl)-1,2,3,4,5,10-hexahydroazepino[3,4-b]indole
Pseudomonas aeruginosa
pH 7.5, 37°C
0.578
ethyl (2E)-3-(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)prop-2-enoate
Trypanosoma brucei
-
pH 7.8, 37°C
0.0021
ethyl 2-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]-2-methylpropanoate
Trypanosoma brucei
-
pH 7.8, 37°C
0.0016
ethyl 2-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]butanoate
Trypanosoma brucei
-
pH 7.8, 37°C
0.0028
ethyl 2-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]propanoate
Trypanosoma brucei
-
pH 7.8, 37°C
0.0167
ethyl 3-(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)propanoate
Trypanosoma brucei
-
pH 7.8, 37°C
1
ethyl 3-(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-7-yl)propanoate
Trypanosoma brucei
-
above, pH 7.8, 37°C
0.0417
ethyl [(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy](phenyl)acetate
Trypanosoma brucei
-
pH 7.8, 37°C
0.0035
ethyl [(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]acetate
Trypanosoma brucei
-
pH 7.8, 37°C
0.0036
methyl [(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]acetate
Trypanosoma brucei
-
pH 7.8, 37°C
0.1
N-(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)-4-nitrobenzene-1-sulfonamide
Staphylococcus aureus
-
prodrug, value above 0.1 mM. pH not specified in the publication, temperature not specified in the publication
0.00066
N-(3-(N-L-leucylsulfamoyl)phenyl)-3,4-dimethoxybenzamide
Trypanosoma brucei
-
pH 7.5, 37°C
0.00025
N-(3-(N-L-leucylsulfamoyl)phenyl)-4-benzyloxybenzamide
Trypanosoma brucei
-
pH 7.5, 37°C
0.0003
N-(3-(N-L-leucylsulfamoyl)phenyl)-4-hydroxybenzamide
Trypanosoma brucei
-
pH 7.5, 37°C
0.00024
N-(3-(N-L-leucylsulfamoyl)phenyl)-4-methoxybenzamide
Trypanosoma brucei
-
pH 7.5, 37°C
0.0777
N-ethyl-2-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]acetamide
Trypanosoma brucei
-
pH 7.8, 37°C
0.1
N-tert-butyl-2-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]acetamide
Trypanosoma brucei
-
above, I114pH 7.8, 37°C
0.0074
tert-butyl [(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]acetate
Trypanosoma brucei
-
pH 7.8, 37°C
0.1
tert-butyl [2-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]ethyl]carbamate
Trypanosoma brucei
-
above, pH 7.8, 37°C
0.1
[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]acetaldehyde
Trypanosoma brucei
-
above, pH 7.8, 37°C
0.1
[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-6-yl)oxy]acetic acid
Trypanosoma brucei
-
above, pH 7.8, 37°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.024
-
mutant A293D, in crude enzyme extract of Escherichia coli strain TG1
0.047
-
purified recombinant wild-type enzyme, with substrate tRNALeu from Escherichia coli
0.14
0.235
-
purified recombinant wild-type enzyme, with substrate tRNALeu from Aquifex aeolicus
0.28
-
wild-type enzyme, in crude enzyme extract of Escherichia coli strain TG1
0.29
-
mutant T252E/M328K, in crude enzyme extract of Escherichia coli strain TG1
1.3
-
purified recombinant wild-type enzyme, with substrate tRNALeu from Aquifex aeolicus
1.5
additional information
0.14
-
mutants A293I, A293G, and A293Y, in crude enzyme extract of Escherichia coli strain TG1
1.5
-
purified recombinant wild-type enzyme, with substrate tRNALeu from Escherichia coli
additional information
-
activiy of several enzyme mutants and mixed mutants, containing subparts of the Escherichia coli enzyme
additional information
-
mischarging and post-transfer editing activities, overview
additional information
-
activiy of several enzyme mutants and mixed mutants, containing subparts of the Escherichia coli enzyme
additional information
-
aminoacid activation activities of wild-type and mutant enzymes
additional information
-
hydrolytic post-transfer editing activity of wild-type and D345A mutant LeuRS CP1 domains, activities of truncation mutants, overview
additional information
-
activity and specificity of several truncation and deletion mutants, overview
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 7.5
7.5
7.6
7.8
8.2
9
-
in Tris-HCl or Bis-Tris-propane-HCl, the activity decreases obviously at pH 8.0 or below
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
37
45
65
additional information
37
-
assay at
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20 - 40
-
20°C: about 30% of maximal activity, 40°C: about 85% of maximal activity, cytoplasmic enzyme
5 - 40
-
5°C: about 35% of maximal activity, 40°C: about 45% of maximal activity, mitochondrial enzyme
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
brenda
-
661109, 661178, 661190, 663351, 672235, 672244, 672264, 674619, 690955, 693628, 703196, 703725, 704689
-
-
brenda
wild-type and temperature-sensitive and leucine-auxotroph mutant leu-5
-
-
brenda
respiratory deficient mutants. The phenotype is a consequence of a mutation in a nuclear gene coding for mitochondrial leucyl-tRNA synthetase
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
transmitochondrial, osteosarcoma-derived (143B.TK-) cybrid cell lines from patients
brenda
-
LARS1 is over-expressed in lung cancer cells compared to control tissue
brenda
LeuRS expression in mammary gland tissue is significantly higher during lactation compared to pregnancy. In pregnancy mammary gland tissue LeuRS showed no difference in the acinar buds and the connective tissue. While in lactating mammary gland tissue, most of LeuRS is expressed in the acinar buds with only a small amount detected in the connective tissue, quantitative real-time PCR expression analysis. the level of LeuRS expression is significantly higher in lactating mammary gland tissue than in pregnancy mammary gland tissue
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
during restricted growth on low levels of leucine, localized in cytoplasmic membrane
-
brenda
-
co-localization of LRS and lysosome-associated membrane glycoprotein 2, LAMP2
brenda
-
2.4% of total activity in the cell, enzyme participates in a large and stable multienzyme complex
brenda
-
during unrestricted growth, localized in this soluble protein
-
brenda
additional information
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major part, enzyme participates in a multienzyme complex, not as large and stable as the one from nucleus
brenda
additional information
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location analysis of LRS with and without leucine, using stimulated emission depletion (STED) microscopy one of the super-resolution microscopy and transmission electron microscopy (TEM), reveals enzyme translocation to the lysosome from cytoplasm on addition of leucine. The translocation is inhibited by treatment with compound BC-LI-0186 disrupting the interaction between RagD and LRS
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brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
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the family of leucyl-tRNA synthetases is divided into prokaryotic and eukaryal/archaeal groups according to the presence and position of specific insertions and extensions. e.g. the LSD1, i.e. leucine-specific domain 1, which is naturally present in eukaryal/archaeal LeuRSs, but absent from prokaryotic LeuRSs. The LSD1s from organisms of both groups are dispensable for post-transfer editing
evolution
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the family of leucyl-tRNA synthetases is divided into prokaryotic and eukaryal/archaeal groups according to the presence and position of specific insertions and extensions. e.g. the LSD1, i.e. leucine-specific domain 1, which is naturally present in eukaryal/archaeal LeuRSs, but absent from prokaryotic LeuRSs. The LSD1s from organisms of both groups are dispensable for post-transfer editing
evolution
based on sequence homology and the structures of the catalytic active sites, aaRSs are divided into two classes of 10 members each. Class I synthetases are further divided into three subclasses, a, b, and c, according to sequence homology. Leucyl-tRNA synthetase (LeuRS) belongs to class I aaRSs that include a typical Rossmann dinucleotide-bindingfold active site architecture with the signature sequence modules HIGH and KMSKS. According to evolutionary models, the primitive catalytic core is extended by the insertion and/or fusion of additional domains (also called modules) in LeuRSs, most of which have inserted a large connective polypeptide 1 (CP1) domain that is responsible for amino acid editing. To ensure translation accuracy, LeuRSs have evolved a mechanism to remove aminoacyl AMP (aa-AMP, pre-transfer editing) and aa-tRNA (post-transfer editing). Although post-transfer editing is carried out by the CP1 domain in most LeuRSs, this domain has been naturally deleted in LeuRS from Mycoplasma mobile (MmLeuRS). Sequence comparisons of the stem contact-fold domain (SC-fold) involved in editing, basic residues on helix alpha3 of the SC-fold are critical for catalytic efficiency, overview
evolution
enzyme leucyl-tRNA synthetase is part of the aminoacyl-tRNA synthetase (aaRS) family
evolution
leucyl-tRNA synthetase (LeuRS) belongs to class Ia aminoacyl-tRNA synthetases (AaRSs). Based on their similar structures, LeuRS, IleRS, and ValRS are collectively known as LIVRS, all of which contain a representative catalytic core consisting of a Rossmann fold. Besides the conservative Rossmann fold, almost all LeuRSs contain a large insertion domain called connective peptide 1 (CP1) within the sequence of the catalytic core. CP1 folds independently in the tertiary structure and is defined as a classic editing domain, in which the aminoacyl bond of mischarged aatRNA is hydrolyzed (post-transfer editing) to ensure the fidelity of the catalytic process
evolution
based on sequence homology and the structures of the catalytic active sites, aaRSs are divided into two classes of 10 members each. Class I synthetases are further divided into three subclasses, a, b, and c, according to sequence homology. Leucyl-tRNA synthetase (LeuRS) belongs to class I aaRSs that include a typical Rossmann dinucleotide-binding fold active site architecture with the signature sequence modules HIGH and KMSKS. According to evolutionary models, the primitive catalytic core is extended by the insertion and/or fusion of additional domains (also called modules) in LeuRSs, most of which have inserted a large connective polypeptide 1 (CP1) domain that is responsible for amino acid editing. To ensure translation accuracy, LeuRSs have evolved a mechanism to remove aminoacyl AMP (aa-AMP, pre-transfer editing) and aa-tRNA (post-transfer editing). Sequence comparisons of the stem contact-fold domain (SC-fold) involved in editing, basic residues on helix alpha3 of the SC-fold are critical for catalytic efficiency, overview
evolution
based on sequence homology and the structures of the catalytic active sites, aaRSs are divided into two classes of 10 members each. Class I synthetases are further divided into three subclasses, a, b, and c, according to sequence homology. Leucyl-tRNA synthetase (LeuRS) belongs to class I aaRSs that include a typical Rossmann dinucleotide-binding fold active site architecture with the signature sequence modules HIGH and KMSKS. According to evolutionary models, the primitive catalytic core is extended by the insertion and/or fusion of additional domains (also called modules) in LeuRSs, most of which have inserted a large connective polypeptide 1 (CP1) domain that is responsible for amino acid editing. To ensure translation accuracy, LeuRSs have evolved a mechanism to remove aminoacyl AMP (aa-AMP, pre-transfer editing) and aa-tRNA (post-transfer editing). Sequence comparisons of the stem contact-fold domain (SC-fold) involved in editing, basic residues on helix alpha3 of the SC-fold are critical for catalytic efficiency, overview
evolution
based on sequence homology and the structures of the catalytic active sites, aaRSs are divided into two classes of 10 members each. Class I synthetases are further divided into three subclasses, a, b, and c, according to sequence homology. Leucyl-tRNA synthetase (LeuRS) belongs to class I aaRSs that include a typical Rossmann dinucleotide-bindingfold active site architecture with the signature sequence modules HIGH and KMSKS. According to evolutionary models, the primitive catalytic core is extended by the insertion and/or fusion of additional domains (also called modules) in LeuRSs, most of which have inserted a large connective polypeptide 1 (CP1) domain that is responsible for amino acid editing. To ensure translation accuracy, LeuRSs have evolved a mechanism to remove aminoacyl AMP (aa-AMP, pre-transfer editing) and aa-tRNA (post-transfer editing). Sequence comparisons of the stem contact-fold domain (SC-fold) involved in editing, basic residues on helix alpha3 of the SC-fold are critical for catalytic efficiency, overview
evolution
based on sequence homology and the structures of the catalytic active sites, aaRSs are divided into two classes of 10 members each. Class I synthetases are further divided into three subclasses, a, b, and c, according to sequence homology. Leucyl-tRNA synthetase (LeuRS) belongs to class I aaRSs that include a typical Rossmann dinucleotide-bindingfold active site architecture with the signature sequence modules HIGH and KMSKS. According to evolutionary models, the primitive catalytic core is extended by the insertion and/or fusion of additional domains (also called modules) in LeuRSs, most of which have inserted a large connective polypeptide 1 (CP1) domain that is responsible for amino acid editing. To ensure translation accuracy, LeuRSs have evolved a mechanism to remove aminoacyl AMP (aa-AMP, pre-transfer editing) and aa-tRNA (post-transfer editing). Sequence comparison of the EcLeuRS stem contact-fold domain (SC-fold) with editing-deficient enzymes suggests that key residues of this module have evolved an adaptive strategy to follow the editing functions of LeuRS, basic residues on helix alpha3 of the SC-fold are critical for catalytic efficiency, overview
evolution
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each member of the archaeal family Sulfolobaceae contains a LeuRS (LeuRS-I) that has a disrupted CP1 editing domain. LeuRS-I appears to be a duplication of a second LeuRS (LeuRS-F) that possesses canonical aminoacylation and CP1 editing domains
evolution
Pyrococcus horikoshii ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3
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based on sequence homology and the structures of the catalytic active sites, aaRSs are divided into two classes of 10 members each. Class I synthetases are further divided into three subclasses, a, b, and c, according to sequence homology. Leucyl-tRNA synthetase (LeuRS) belongs to class I aaRSs that include a typical Rossmann dinucleotide-bindingfold active site architecture with the signature sequence modules HIGH and KMSKS. According to evolutionary models, the primitive catalytic core is extended by the insertion and/or fusion of additional domains (also called modules) in LeuRSs, most of which have inserted a large connective polypeptide 1 (CP1) domain that is responsible for amino acid editing. To ensure translation accuracy, LeuRSs have evolved a mechanism to remove aminoacyl AMP (aa-AMP, pre-transfer editing) and aa-tRNA (post-transfer editing). Sequence comparisons of the stem contact-fold domain (SC-fold) involved in editing, basic residues on helix alpha3 of the SC-fold are critical for catalytic efficiency, overview
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evolution
[Mycoplasma] mobile ATCC 43663 / 163K / NCTC 11711
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based on sequence homology and the structures of the catalytic active sites, aaRSs are divided into two classes of 10 members each. Class I synthetases are further divided into three subclasses, a, b, and c, according to sequence homology. Leucyl-tRNA synthetase (LeuRS) belongs to class I aaRSs that include a typical Rossmann dinucleotide-bindingfold active site architecture with the signature sequence modules HIGH and KMSKS. According to evolutionary models, the primitive catalytic core is extended by the insertion and/or fusion of additional domains (also called modules) in LeuRSs, most of which have inserted a large connective polypeptide 1 (CP1) domain that is responsible for amino acid editing. To ensure translation accuracy, LeuRSs have evolved a mechanism to remove aminoacyl AMP (aa-AMP, pre-transfer editing) and aa-tRNA (post-transfer editing). Although post-transfer editing is carried out by the CP1 domain in most LeuRSs, this domain has been naturally deleted in LeuRS from Mycoplasma mobile (MmLeuRS). Sequence comparisons of the stem contact-fold domain (SC-fold) involved in editing, basic residues on helix alpha3 of the SC-fold are critical for catalytic efficiency, overview
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malfunction
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replacement of Giardia lamblia eukarya-specific insertion 1, GlESI, by human eukarya-specific insertion 1, HsESI, impairs leucine activation, aminoacylation and post-transfer editing functions without changing the editing specificity
malfunction
abrogation of the LeuRS specificity determinant threonine 252 does not improve the affinity of the editing site for the cognate leucine as expected, but instead substantially enhances the rate of leucyl-tRNALeu hydrolysis. Molecular dynamics simulations reveals that the wild-type enzyme, but not the T252A mutant, enforces leucine to adopt the side-chain conformation that promotes the steric exclusion of a putative catalytic water
malfunction
mutations in mitochondrial DNA determine important human diseases. The majority of the known pathogenic mutations are located in transfer RNA (tRNA) genes and are responsible for a wide range of currently untreatable disorders. The detrimental effects of mt-tRNA point mutations can be attenuated by increasing the expression of the cognate mt-aminoacyl-tRNA synthetases (aaRSs). The isolated C-terminal domain of human mt-leucyl-tRNA synthetase (LeuRS-Cterm) localizes to mitochondria and ameliorates the energetic defect in trans-mitochondrial cybrids carrying mutations either in the cognate mt-tRNALeu(UUR) or in the non-cognate mt-tRNAIle gene.Since the mt-LeuRS-Cterm does not possess catalytic activity, its rescuing ability is most likely mediated by a chaperon-like effect, consisting in the stabilization of the tRNA structure altered by the mutation
malfunction
the C-terminal domain of human mt leucyl-tRNA synthetase is both necessary and sufficient to improve the pathologic phenotype associated either with these mild mutations or with the severe m.3243A>G mutation in the mt-tRNALeu(UUR) gene, overview. The small, non-catalytic domain is able to directly and specifically interact in vitro with human mt-tRNALeu(UUR) with high affinity and stability and, with lower affinity, with mt-tRNAIle. The carboxyterminal domain of human mt leucyl-tRNA synthetase can be used to correct mt dysfunctions caused by mt-tRNA mutations. The Cterm domain of human mt-LeuRS directly interacts with mt-tRNALeu(UUR) and mt-tRNAIle in vitro
malfunction
Lars knockdown does not decrease phosphorylated mTOR in differentiated myotubes, nor does it affect the hypertrophy of myotubes. Extracellular flux analysis shows that Lars knockdown does not affect the metabolism (glycolysis and mitochondrial respiration) of myotubes
malfunction
knockdown of LRS in HEK-293 cells results in impaired leucine-stimulated S6K1 phosphorylation, total amino acid stimulation of pS6K1 is also significantly reduced. Knockdown of LRS decreasesVps34 activity induced by leucine or total amino acids. Knockdown of LRS does not affect the protein levels of mTOR, raptor, Vps34, and Rag GTPases
malfunction
siRNA-mediated knockdown of LeuRS leads to suppression of rapamycin (mTOR), p-mTOR, ribosomal protein S6 kinase 1 (S6K1), p-S6K1, beta-casein, sterol regulatory element binding-protein 1c (SREBP-1c), glucose transporter 1 (GLUT1), and cyclin D1 mRNA and protein expression. LeuRS knockdown reduces cell growth, the expression of lactation-associated proteins, and milk synthesis
malfunction
mutation of highly conserved basic residues on the third alpha-helix of the KMSKS catalytic loop domain impairs the affinity of LeuRS for the anticodon stem of tRNALeu, which decreases both aminoacylation and editing activities
metabolism
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isoform LeuRS1 generates Leu-tRNALeu for protein biosynthesis and exhibits obvious post-transfer editing activity to prevent generation of mischarged tRNALeu
metabolism
mTORC1 lysosomal translocation and activation in response to amino acids requires the GTP-bound form of RagA or B as well as the GDP-bound form of RagC or D. The Ragulator complex and the GATOR1 complex act as GEF (guanine nucleotide exchange factor) and GAP (GTPase activating protein) for RagA/B, respectively. Role of LRS as a leucine sensor upstream of TORC1. Two other tRNA synthetases, IRS (isoleucyl-tRNA synthetase) and EPRS (glutamyl-prolyl-tRNA synthetase), are both in the multi-tRNA synthetase complex together with enzyme LRS, but both have no effect on leucine-stimulated Vps34 activity. LRS directly regulates Vps34 activity
metabolism
LRS-RagD interaction plays a pivotal role in the nutrientdependent mTORC1 signalling pathway
metabolism
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the LeuAC active site accommodates two ATP conformations, accounting for successive, in situ phosphorylation of the bound leucyl-5'AMP phosphate, accounting for ADP production. This ATP consumption regenerates the transition state for amino acid activation
metabolism
large conformational changes accompany Leu-AMP formation, with a peptide-plane flip driving global conformational changes. The CP1 hairpin swing is mediated by L550-E169 partnership
metabolism
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isoform LeuRS1 generates Leu-tRNALeu for protein biosynthesis and exhibits obvious post-transfer editing activity to prevent generation of mischarged tRNALeu
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metabolism
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large conformational changes accompany Leu-AMP formation, with a peptide-plane flip driving global conformational changes. The CP1 hairpin swing is mediated by L550-E169 partnership
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physiological function
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leucyl-tRNA synthetase is an essential RNA splicing factor for yeast mitochondrial introns. RNA deletion mutants of the large bI4 intron are active in RNA splicing and the activity of the minimized bI4 intron is enhanced in vitro by the presence of the bI4 maturase or LeuRS
physiological function
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the A3243G mutation of the tRNALeu gene causes mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms and 2% of cases of type 2 diabetes. The alteration of aminoacylation of tRNALeu(UUR) caused by the A3243G mutation leads to mitochondrial translational defects and thereby reduces the aminoacylating efficiencies of tRNALeu(UUR) as well as of tRNAAla and tRNAMet
physiological function
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existence of a tRNA-independent pretransfer editing pathway in leucyltRNA synthetases from Aquifex aeolicus. This editing pathway is distinct from the post-transfer editing site and may occur at the synthetic catalytic site
physiological function
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aminoacyl-tRNA synthetases are critical for the translational process, catalyzing the attachment of specific amino acids to their cognate tRNAs. To ensure formation of the correct aminoacyl-tRNA, and thereby enhance the reliability of translation, several aminoacyl-tRNA synthetases have an editing capability that hinders formation of misaminoacylated tRNAs, analysis of the mechanism of the editing reaction for class I enzyme leucyl-tRNA synthetase complexed with a misaminoacylated tRNALeu by initio hybrid quantum mechanical/molecular mechanical potentials in conjunction with molecular dynamics simulations, overview. Editing is a self-cleavage reaction of the tRNA and so it is the tRNA, and not the protein, that drives the reaction. The protein does, however, have an important stabilizing effect on some high-energy intermediates along the reaction path, which is more efficient than the ribozyme would be alone. This indicates that editing is achieved by a hybrid ribozyme/protein catalyst. The water molecule that acts as the nucleophile in the editing reaction is activated by a 3'-hydroxyl group at the 3'-end of tRNALeu and that the O2' atom of the leaving group of the substrate is capped by one of the water's hydrogen atoms
physiological function
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aminoacyl-tRNA synthetases have evolved editing mechanisms to hydrolyze misactivated amino acids (pre-transfer editing) or misacylated tRNAs (post-transfer editing). Class Ia leucyl-tRNA synthetase may misactivate various natural and non-protein amino acids and then mischarge tRNALeu. The fidelity of prokaryotic LeuRS depends on multiple editing pathways to clear the incorrect intermediates and products in every step of aminoacylation reaction. Post-transfer editing as a final checkpoint of the reaction is very important to prevent mis-incorporation in vitro
physiological function
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the enzyme naturally produces mischarged tRNALeu
physiological function
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the enzyme plays a critical role in amino acid-induced mammalian target of rapamycin C1 activation by sensing intracellular leucine concentration and initiating molecular events leading to mammalian target of rapamycin C1 activation. The enzyme directly binds to Rag GTPase, the mediator of amino acid signaling to mTORC1, in an amino acid-dependent manner and functions as a GTPase-activating protein for Rag GTPase to activate mammalian target of rapamycin C1
physiological function
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the enzyme is a leucine sensor for serine/threonine kinase TORC1 and interacts with Gtr1
physiological function
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the enzyme is a leucine sensor for serine/threonine kinase TORC1 and interacts with Gtr2
physiological function
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the enzyme naturally produces mischarged tRNALeu
physiological function
aminoacyl-tRNA synthetases (aaRSs) are a large and diverse family of enzymes that catalyze the attachment of amino acids to their cognate tRNAs in a two-step aminoacylation reaction as follows: 1. amino acid activation by ATP hydrolysis to form an aminoacyl-adenylate intermediate, and 2. transfer of the aminoacyl moiety from the intermediate to the cognate tRNA isoacceptor to form aminoacyl-tRNA (aa-tRNA)
physiological function
Escherichia coli leucyl-tRNA synthetase (LeuRS) is an essential multi-domain metalloenzyme that aminoacylates tRNALeu with leucine. Enzyme LeuRS is an essential enzyme that relies on specialized domains to facilitate the aminoacylation reaction. Structural changes within the ZN-1 domain play a central role in LeuRS's catalytic cycle. The enzyme performs a Zn2+ dependent translocation mechanism for charged tRNALeu, Zn2+ is an architectural cornerstone of the ZN-1 domain and that without its geometric coordination the domain collapses. Residues C159, C176 and C179 coordinate Zn2+ and that this interaction is essential for leucylation to occur, but is not essential for deacylation
physiological function
the ligation of amino acid to tRNA for purposes of protein synthesis proceeds in two steps, bothcatalyzed by a corresponding aminoacyl-tRNA synthetase(aaRS). The amino acid is first activated to anaminoacyl-adenylate (aa-AMP) intermediate at theexpense of ATP, followed by the transfer of aminoacylmoiety to the 2'- or 3'-OH groups at the terminal ribose of the cognate tRNA. Both steps occurwithin the same synthetic/aminoacylation active site located in thecatalytic aaRS domain. Based on the topology of the catalytic domains, the conserved recognition peptides and interaction with the tRNA, aaRSs can be divided into two classes, I and II. The mechanisms of aminoacylation and editing are basically conserved among the classes, although some class-specific features have been recognized. Editing aaRSs exercise specificity through a double-selection mechanism that uses structural/chemical differences between the cognate and non-cognate amino acids twice but in different ways. Leu-tRNALeu is excluded from proofreading basically at the level of catalysis, not binding. This is accomplished by the side chain of the cognate leucine, which adopts a conformation that sterically precludes the positioning of a water nucleophile near the tRNA-assisted hydrolytic machinery. The A76 3'-OH group is a crucial residue in the positioning and activation of the catalytic water. Deacylation mechanism of the enzyme, simulation and modeling, overview
physiological function
leucyl-tRNA synthetases (LeuRSs) catalyze the linkage of leucine with tRNALeu
physiological function
leucyl-tRNA synthetase (Lars) is an intracellular sensor of leucine involved in the activation of mTOR signaling with a physiological role in skeletal muscle cells, potential roles of Lars for the activation of mTOR signaling, skeletal muscle cell differentiation, hypertrophy, and metabolism. Enzyme Lars directly binds to Rag GTPase, a known mediator of amino acid signaling to mTORC1, in a leucine-dependent manner and acts as a GTPase-activating protein for Rag GTPase to activate mTOR signaling. Lars is required for skeletal muscle differentiation through the activation of mTOR signaling, but not for hypertrophy or metabolic alteration of myotubes, link between Lars and mTOR activation in muscle cells and the physiological role of myoblast differentiation. Lars is essential for the activation of mTOR signaling in skeletal muscle cells and myogenic differentiation thought the induction of Igf2 expression
physiological function
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leucyl-tRNA synthetase (LRS) plays major roles in providing leucine-tRNA and activating mechanistic target of rapamycin complex 1 (mTORC1) through intracellular leucine sensing. mTORC1 activated by amino acids affects the influence on physiology functions including cell proliferation, protein synthesis and autophagy in various organisms. Crosstalk between leucine sensing, LRS translocation, RagD interaction, and mTORC1 activation, mTORC1 activation is related to LRS translocation dependent on leucine, analysis of relationship between mTORC1 activation and LRS translocation, overview
physiological function
leucyl-tRNA synthetase (LRS) is a leucine sensor for the activation of Vps34-PLD1 upstream of mTORC1. LRS binds to RagD-GTP, and forms a LRS-RagD complex, which translocates mTORC1 from the cytosol to the lysosome surface for subsequent activation of the mTORC1 signalling pathway. LRS is necessary for amino acid-induced Vps34 activation, cellular phosphatidylinositol-3-phosphate level increase, PLD1 activation, and PLD1 lysosomal translocation. Leucine binding but not tRNA charging activity of LRS is required for this regulation. LRS directly interacts with Vps34 in a non-autophagic complex, and activates Vps34 kinase activity in a leucine-dependent manner. Vps34 and PLD1 are required to mediate LRS activation of mTORC1. Only non-autophagic Vps34 complexes are involved in amino acid signaling to mTOR. LRS is necessary for amino acid activation of PLD1. Overexpression of LRS enhanced amino acid activation of S6K1
physiological function
the direct interaction between enzyme LRS and RagD activates mTORC1 in live cells under leucine-deprived conditions. The nutrient sensing mechanism of mTORC1, particularly for Leu, an essential biomarker for nutrient status in cellular systems, is regulated by protein-protein interactions between LRS and RagD and directly mediate mTORC1 activation
physiological function
leucyl-tRNA synthetase regulates lactation and cell proliferation via mTOR signaling in dairy cow mammary epithelial cells, role of LeuRS as an intracellular L-leucine sensor for the mTORC1 pathway. LeuRS up-regulates the mTOR pathway to promote proliferation and lactation of dairy cow mammary epithelial cells (DCMECs) in response to changes in the intracellular leucine concentration. Treatment with L-leucine increases DCMECs viability and proliferation, as well as mammalian target of rapamycin (mTOR), p-mTOR, ribosomal protein S6 kinase 1 (S6K1), p-S6K1, beta-casein, sterol regulatory element binding-protein 1c (SREBP-1c), glucose transporter 1 (GLUT1), and cyclin D1 mRNA and protein expression via activity of enzyme LeuRS. Secretion of lactose and triglyceride are also increased. Effect of leucine on LeuRS to regulate cell growth and expression of proteins involved in mTOR signaling in DCMECs
physiological function
aminoacyl-tRNA synthetases (aaRSs) are a large and diverse family of enzymes that catalyze the attachment of amino acids to their cognate tRNAs in a two-step aminoacylation reaction as follows: 1. amino acid activation by ATP hydrolysis to form an aminoacyl-adenylate intermediate, and 2. transfer of the aminoacyl moiety from the intermediate to the cognate tRNA isoacceptor to form aminoacyl-tRNA (aa-tRNA)
physiological function
aminoacyl-tRNA synthetases (aaRSs) are a large and diverse family of enzymes that catalyze the attachment of amino acids to their cognate tRNAs in a two-step aminoacylation reaction as follows: 1. amino acid activation by ATP hydrolysis to form an aminoacyl-adenylate intermediate, and 2. transfer of the aminoacyl moiety from the intermediate to the cognate tRNA isoacceptor to form aminoacyl-tRNA (aa-tRNA)
physiological function
aminoacyl-tRNA synthetases (aaRSs) are a large and diverse family of enzymes that catalyze the attachment of amino acids to their cognate tRNAs in a two-step aminoacylation reaction as follows: 1. amino acid activation by ATP hydrolysis to form an aminoacyl-adenylate intermediate, and 2. transfer of the aminoacyl moiety from the intermediate to the cognate tRNA isoacceptor to form aminoacyl-tRNA (aa-tRNA)
physiological function
aminoacyl-tRNA synthetases (aaRSs) are a large and diverse family of enzymes that catalyze the attachment of amino acids to their cognate tRNAs in a two-step aminoacylation reaction as follows: 1. amino acid activation by ATP hydrolysis to form an aminoacyl-adenylate intermediate, and 2. transfer of the aminoacyl moiety from the intermediate to the cognate tRNA isoacceptor to form aminoacyl-tRNA (aa-tRNA)
physiological function
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isoform LeuRS-I is deficient in residues critical for editing, it is required for optimal growth. Isoform LeuRS-F is essential for viability
physiological function
in leukocytes, a specific exon skipping event leads to splice variant LSV3 which is regulated by serine-arginine-rich splicing factor 1. LSV3 has a 71 amino acid deletion in the catalytic domain and lacks tRNA leucylation activity in vitro. LSV3 splice variant retains its role as a leucine sensor and signal transducer for the proliferation-promoting mTOR kinase
physiological function
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preparation of an urzyme LeuAC, i.e. about 120-130 amino acids excerpted from regions where genetic coding sequence complementarities have been identified. The protein catalyzes amino acid activation and tRNALeu aminoacylation. Mutation of the three active-site lysine residues to alanine causes significant, but modest reduction in both amino acid activation and aminoacylation. LeuAC catalyzes production of ADP
physiological function
leucine is required for cell proliferation of tuberous sclerosis complex-null cells through the activation of leucyl-tRNA synthetase (LARS1)-mTORC1 pathway. Cell proliferation and survival are attenuated by LARS1 knock-down or inhibitors in tuberous sclerosis complex-null cells. Either rapamycin or LARS1 inhibitors significantly decrease colony formation ability while their combined treatment drastically attenuates it
physiological function
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leucine-dependent mTORC1 activation depends on GTPase activating protein events mediated by LRS. Inhibition of the LRS-RagD GTPase interaction interfere with the mTORC1 signaling pathway
physiological function
LarSb mutation causes infantile liver failure syndrome ILFS1-like phenotype in zebrafish. In a loss-of-function mutant, the proliferation ability of liver is drastically decreased at later stages accompanied with severe DNA damage. The mTORC1 signaling is hyperactivated in the mutant
physiological function
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LRS negatively regulates myoblast differentiation in vitro, independent of its regulation of protein synthesis, and it requires leucine-binding but not tRNA charging activity of LRS. In a mouse injury model, local knock down of LRS accelerates muscle regeneration. A Rag-mTORC1 pathway is the mediator of the nontranslational function of LRS in myogenesis
physiological function
LARS1 is involved in glucose-dependent control of leucine usage. Upon glucose starvation, LARS1 is phosphorylated by Unc-51 like autophagy activating kinase ULK1 at the residues crucial for leucine binding. The phosphorylated LARS1 shows decreased leucine binding. ULK1 may phosphorylate LARS1 at S391 first and then S720 in glucose deprivation
physiological function
Pyrococcus horikoshii ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3
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aminoacyl-tRNA synthetases (aaRSs) are a large and diverse family of enzymes that catalyze the attachment of amino acids to their cognate tRNAs in a two-step aminoacylation reaction as follows: 1. amino acid activation by ATP hydrolysis to form an aminoacyl-adenylate intermediate, and 2. transfer of the aminoacyl moiety from the intermediate to the cognate tRNA isoacceptor to form aminoacyl-tRNA (aa-tRNA)
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physiological function
[Mycoplasma] mobile ATCC 43663 / 163K / NCTC 11711
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aminoacyl-tRNA synthetases (aaRSs) are a large and diverse family of enzymes that catalyze the attachment of amino acids to their cognate tRNAs in a two-step aminoacylation reaction as follows: 1. amino acid activation by ATP hydrolysis to form an aminoacyl-adenylate intermediate, and 2. transfer of the aminoacyl moiety from the intermediate to the cognate tRNA isoacceptor to form aminoacyl-tRNA (aa-tRNA)
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additional information
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the CP1, i.e. connective peptide 1, domain of LeuRS contains the editing active site ESI, eukarya-specific insertion 1, Thr341 serves as a specificity discriminator. Arg338 is crucial for tRNALeu charging and the Asp440 is crucial for leucine activation and aminoacylation. The post-transfer editing required the C-terminal domain, Arg338 and Asp440 of GlLeuRS
additional information
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leucine-specific domain 1, LSD1, is dispensable for post-transfer editing
additional information
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leucine-specific domain 1, LSD1, is dispensable for post-transfer editing
additional information
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human leucyl-tRNA synthetase and mitochondrial protein elongation factor EF-Tu show suppressing cross-activity on different tRNA mutants in humans and Saccharomyces cerevisiae, mechanism and specificity of suppression, overview. Suppressive activities of wild-type and mutant enzymes, overview
additional information
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activating role of C-terminal domain in the reactions of aminoacylation and editing, and its contribution to interaction with tRNALeu, overview. The C-terminal domain does is not critical for the manifestation of specificity of the enzyme of homologous RNAs, but is required for to enhance the rate of catalysis in aminoacylation and editing reaction
additional information
the KMSKS catalytic loop exhibits alpha-alpha-beta-alpha topology in class Ia and Ib aminoacyl-tRNA synthetases. Incorporation of acidic residues on the beta-strand stimulates the tRNA-dependent editing activity of the chimeric minimalist enzyme Mycoplasma mobile LeuRS fused to the connective polypeptide 1 editing domain and leucine-specific domain from EcLeuRS, acidic residues on the beta-strand enhance the editing activity of EcLeuRS and sense the size of the tRNALeu D-loop
additional information
enzyme structure homology modeling using the structure of Thermus thermophilus LeuRS, PDB ID 2V0C, as template
additional information
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enzyme structure homology modeling using the structure of Thermus thermophilus LeuRS, PDB ID 2V0C, as template
additional information
there are two catalytic sites, the leucylation site housed within the aminoacylation domain and the hydrolytic deacylation site housed within the CP1 editing domain, the ZN-1 domain is known to play an essential structural role in stabilizing the Leu-Amp adenylate. Structural analysis of LeuRS enzymes using Fourier transform infrared spectroscopy (FTIR), and homology modeling of LeuRS in the editing conformation, visualizing the ZN-1 domain, by using the structure in editing conformation of the LeuRS enzyme from Thermus thermophilus, PDB ID 1OBH as template, overview
additional information
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there are two catalytic sites, the leucylation site housed within the aminoacylation domain and the hydrolytic deacylation site housed within the CP1 editing domain, the ZN-1 domain is known to play an essential structural role in stabilizing the Leu-Amp adenylate. Structural analysis of LeuRS enzymes using Fourier transform infrared spectroscopy (FTIR), and homology modeling of LeuRS in the editing conformation, visualizing the ZN-1 domain, by using the structure in editing conformation of the LeuRS enzyme from Thermus thermophilus, PDB ID 1OBH as template, overview
additional information
in silico models of the wild-type and mutated LeuRS CP1 editing domain bound to the analogues with an ester linkage between the amino acid and adenosine as in real substrates [2'-L-leucyladenosine (Leu2A) and 2?-L-norvalyladenosine (Nva2A)] are constructed based on the structure of T252A LeuRS in a complex with tRNALeu and leucyl-adenylate sulphamoyl analogue (Leu-AMS), both positioned in the synthetic active site, and Leu2AA located in the editing domain. The tRNA body dominates the binding energetics of aa-tRNA:LeuRS complex formation
additional information
-
in silico models of the wild-type and mutated LeuRS CP1 editing domain bound to the analogues with an ester linkage between the amino acid and adenosine as in real substrates [2'-L-leucyladenosine (Leu2A) and 2?-L-norvalyladenosine (Nva2A)] are constructed based on the structure of T252A LeuRS in a complex with tRNALeu and leucyl-adenylate sulphamoyl analogue (Leu-AMS), both positioned in the synthetic active site, and Leu2AA located in the editing domain. The tRNA body dominates the binding energetics of aa-tRNA:LeuRS complex formation
additional information
the CP1 hairpin editing structure, residue R236 to G256, and the flexibility of small residues and the charge of polar residues in the CP1 hairpin are crucial for the function of LeuRS. The CP1 hairpin domain is crucial for activities of leucine, leucylation of tRNALeu, and tRNA binding of hcLeuRS
additional information
-
the CP1 hairpin editing structure, residue R236 to G256, and the flexibility of small residues and the charge of polar residues in the CP1 hairpin are crucial for the function of LeuRS. The CP1 hairpin domain is crucial for activities of leucine, leucylation of tRNALeu, and tRNA binding of hcLeuRS
additional information
analysis of the bacterial LeuRS structures (PDB IDs 2BTE and 4AS1) reveals that the isolated C-terminal domain of human mt-leucyl-tRNA synthetase (LeuRS-Cterm) interacts with the elbow region of the cognate tRNA and establishes a higher number of contacts with the sugar-phosphate backbone than with nucleotide-specific chemical groups, preferred interaction of human mt-LeuRS-Cterm with ribose and phosphate oxygen atoms
additional information
-
analysis of the bacterial LeuRS structures (PDB IDs 2BTE and 4AS1) reveals that the isolated C-terminal domain of human mt-leucyl-tRNA synthetase (LeuRS-Cterm) interacts with the elbow region of the cognate tRNA and establishes a higher number of contacts with the sugar-phosphate backbone than with nucleotide-specific chemical groups, preferred interaction of human mt-LeuRS-Cterm with ribose and phosphate oxygen atoms
additional information
three human mitochondrial aminoacyl-tRNA syntethases, namely leucyl-, valyl-, and isoleucyl-tRNA synthetase are able to improve both viability and bioenergetic proficiency of human transmitochondrial cybrid cells carrying pathogenic mutations in the mt-tRNAIle gene
additional information
-
three human mitochondrial aminoacyl-tRNA syntethases, namely leucyl-, valyl-, and isoleucyl-tRNA synthetase are able to improve both viability and bioenergetic proficiency of human transmitochondrial cybrid cells carrying pathogenic mutations in the mt-tRNAIle gene
additional information
small-molecule protein-protein interactions modulators between LRS and RagD can be used as powerful research tools for studying the nutrient-dependent activation of mTORC1 and the subsequent biological outcome
additional information
the KMSKS catalytic loop exhibits alpha-alpha-beta-alpha topology in class Ia and Ib aminoacyl-tRNA synthetases, two glycine residues on the third alpha-helix contribute to flexibility, leucine activation, and editing of LeuRS from Escherichia coli (EcLeuRS), acidic residues on the beta-strand enhance the editing activity of EcLeuRS and sense the size of the tRNALeu D-loop. Incorporation of acidic residues on the beta-strand stimulates the tRNA-dependent editing activity of the chimeric minimalist enzyme Mycoplasma mobile LeuRS fused to the connective polypeptide 1 editing domain and leucine-specific domain from EcLeuRS. Sequence comparison of the EcLeuRS stem contact-fold domain with editing-deficient enzymes suggests that key residues of this module have evolved an adaptive strategy to follow the editing functions of LeuRS. Amino acid residues Arg668 or Arg672 are not involved in the amino acid activation step but rather the second tRNA transfer step
additional information
-
the KMSKS catalytic loop exhibits alpha-alpha-beta-alpha topology in class Ia and Ib aminoacyl-tRNA synthetases, two glycine residues on the third alpha-helix contribute to flexibility, leucine activation, and editing of LeuRS from Escherichia coli (EcLeuRS), acidic residues on the beta-strand enhance the editing activity of EcLeuRS and sense the size of the tRNALeu D-loop. Incorporation of acidic residues on the beta-strand stimulates the tRNA-dependent editing activity of the chimeric minimalist enzyme Mycoplasma mobile LeuRS fused to the connective polypeptide 1 editing domain and leucine-specific domain from EcLeuRS. Sequence comparison of the EcLeuRS stem contact-fold domain with editing-deficient enzymes suggests that key residues of this module have evolved an adaptive strategy to follow the editing functions of LeuRS. Amino acid residues Arg668 or Arg672 are not involved in the amino acid activation step but rather the second tRNA transfer step
additional information
[Mycoplasma] mobile ATCC 43663 / 163K / NCTC 11711
-
the KMSKS catalytic loop exhibits alpha-alpha-beta-alpha topology in class Ia and Ib aminoacyl-tRNA synthetases. Incorporation of acidic residues on the beta-strand stimulates the tRNA-dependent editing activity of the chimeric minimalist enzyme Mycoplasma mobile LeuRS fused to the connective polypeptide 1 editing domain and leucine-specific domain from EcLeuRS, acidic residues on the beta-strand enhance the editing activity of EcLeuRS and sense the size of the tRNALeu D-loop
-
additional information
Mycobacterium tuberculosis ATCC 25618 / H37Rv
-
enzyme structure homology modeling using the structure of Thermus thermophilus LeuRS, PDB ID 2V0C, as template
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Show AA Sequence and Transmembrane Helices (34486 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
100000
107600
116000
1200000
129000
135000
150000
34000
-
x * 34000, N-terminal peptide after cleavage of peptide bond E292-A293, SDS-PAGE, x * 63000, C-terminal peptide after cleavage of peptide bond E292-A293, SDS-PAGE, x * 97300, recombinant wild-type enzyme, SDS-PAGE
35000
63000
65000
97300
-
x * 34000, N-terminal peptide after cleavage of peptide bond E292-A293, SDS-PAGE, x * 63000, C-terminal peptide after cleavage of peptide bond E292-A293, SDS-PAGE, x * 97300, recombinant wild-type enzyme, SDS-PAGE
additional information
-
a series of molecular modeling studies including homology modeling and automated docking simulations are carried out. A 3D structure of Escherichia coli LeuRS is constructed via homology modling using the X-ray structure of Thermus thermophilus as a template because the LeuRS structure of Escherichia coli is not available from X-ray or NMR studies
100000
-
complexed recombinant leuS' and leuS gene product, i.e. alpha/beta-subunit complex, gel filtration
1200000
-
containing 9 amino acyl-tRNA synthetases specific for Glu, Pro, Ile, Leu, Gln, Lys, Arg and Asp
129000
-
x * 129000 + x * ?, SDS-PAGE, the 129000 MW polypeptide is a component of the high-MW aminoacyl-tRNA synthetase complex (MW 1200000, gel filtration)
35000
-
heterodimer in quartenary structure, 2 * 35000, leuS gene product or beta-subunit, + 2 * 65000, leuS gene product or alpha-subunit, SDS-PAGE
35000
-
heterodimer in quartenary structure, 2 * 35000, leuS gene product, + 2 * 65000, leuS gene product, SDS-PAGE
63000
-
2 * 63000, gel electrophoresis, after dissociation, the enzyme exhibits an equilibrium between an active dimeric form and an inactive monomeric form
63000
-
x * 34000, N-terminal peptide after cleavage of peptide bond E292-A293, SDS-PAGE, x * 63000, C-terminal peptide after cleavage of peptide bond E292-A293, SDS-PAGE, x * 97300, recombinant wild-type enzyme, SDS-PAGE
65000
-
heterodimer in quartenary structure, 2 * 35000, leuS gene product or beta-subunit, + 2 * 65000, leuS gene product or alpha-subunit, SDS-PAGE
65000
-
heterodimer in quartenary structure, 2 * 35000, leuS gene product, + 2 * 65000, leuS gene product, SDS-PAGE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
monomer
tetramer
additional information
?
-
x * 129000 + x * ?, SDS-PAGE, the 129000 MW polypeptide is a component of the high-MW aminoacyl-tRNA synthetase complex (MW 1200000, gel filtration)
?
-
the multienzyme complex is composed of 10 distinct polypeptides with MW ranging from 18000 to 165000
?
-
in mammalia and higher eukaryotes: multienzyme complex containing 9 amino acyl-tRNA synthetases specific for Glu, Pro, Ile, Leu, Gln, Lys, Arg and Asp
?
-
x * 34000, N-terminal peptide after cleavage of peptide bond E292-A293, SDS-PAGE, x * 63000, C-terminal peptide after cleavage of peptide bond E292-A293, SDS-PAGE, x * 97300, recombinant wild-type enzyme, SDS-PAGE
?
-
prokaryotes and lower eukaryotes: the corresponding enzymes behave as free enzymes
?
-
in mammalia and higher eukaryotes: multienzyme complex containing 9 amino acyl-tRNA synthetases specific for Glu, Pro, Ile, Leu, Gln, Lys, Arg and Asp
?
-
the isolated CP1 domain of LeuRS is an active protein for editing mischarged tRNALeu(AAG). An insertion of 49 amino acid residues within the CP1 domain, the so-called 49-amino acid motif, is important for the optimal aminoacylation activity of LeuRS and is crucial for the editing capacity of LeuRS-CP1
?
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in mammalia and higher eukaryotes: multienzyme complex containing 9 amino acyl-tRNA synthetases specific for Glu, Pro, Ile, Leu, Gln, Lys, Arg and Asp
?
-
high molecular mass aminoacyl-tRNA synthetase complex with a coherent structure that can be visualized by electron microscopy
dimer
-
(alphabeta) heterodimer with a large extra domain, the leucine-specific domain, inserted into the catalytic domain, the subunit split site is exactly in the middle of the leucine-specific domain and may have a unique function, two peptides of eight and nine amino acid residues in the domain located in the alpha subunit are essential for the enzymes activity
dimer
-
2 * 63000, gel electrophoresis, after dissociation, the enzyme exhibits an equilibrium between an active dimeric form and an inactive monomeric form
tetramer
-
heterodimer in quartenary structure, 2 * 35000, leuS' gene product, + 2 * 65000, leuS gene product, SDS-PAGE
tetramer
-
heterodimer in quartenary structure, 2 * 35000, leuS' gene product or beta-subunit, + 2 * 65000, leuS gene product or alpha-subunit, SDS-PAGE
additional information
-
class I enzyme with unique heterodimeric quartenary structure
additional information
-
determination od secondary structure elements in the enzyme and the isolated beta-subunit
additional information
-
determination of secondary structure elements in the wild-type and mutant enzyme
additional information
-
the amino acid editing site for LeuRS resides within the homologous CP1 domain: threonine-rich peptide and a second conserved GTG region that are separated by about 100 amino acids comprise parts of the hydrolytic editing site, comparison to IleRS, tertiary and primary structure analysis of the amino acid editing site, overview
additional information
-
primary and tertiary structures of the LeuRS unique C-terminal domain, overview, the C-terminal extension of about 60 amino acids forms a discrete domain, which is unique among the LeuRSs and interacts with the corner of the L-shaped tRNALeu, overview
additional information
structure comparison of the Zn-1 domain in editing and in aminoacylation conformations, overview
additional information
-
structure comparison of the Zn-1 domain in editing and in aminoacylation conformations, overview
additional information
-
three-dimensional LeuRS structure and sequence alignment of different eukaryal and archaeal LSD1s, overview
additional information
enzyme LeuRS contains a catalysis domain (aminoacylation) and a CP1 domain (editing). CP1, residue R236 to G256, is inserted 35 A away from the aminoacylation domain. Aminoacylation and editing require CP1 to swing to the coordinated conformation. The neck between the CP1 domain and the aminoacylation domain is defined as the CP1 hairpin. The location of the CP1 hairpin suggests a crucial role in the CP1 swing and domain-domain interaction. Besides the conservative Rossmann fold, almost all LeuRSs contain a large insertion domain called connective peptide 1 (CP1) within the sequence of the catalytic core. CP1 folds independently in the tertiary structure and is defined as a classic editing domain, in which the aminoacyl bond of mischarged aatRNA is hydrolyzed (post-transfer editing) to ensure the fidelity of the catalytic process. Primary sequence and tertiary structure of the CP1 hairpin of LeuRS, and structure-function relationship, overview
additional information
-
enzyme LeuRS contains a catalysis domain (aminoacylation) and a CP1 domain (editing). CP1, residue R236 to G256, is inserted 35 A away from the aminoacylation domain. Aminoacylation and editing require CP1 to swing to the coordinated conformation. The neck between the CP1 domain and the aminoacylation domain is defined as the CP1 hairpin. The location of the CP1 hairpin suggests a crucial role in the CP1 swing and domain-domain interaction. Besides the conservative Rossmann fold, almost all LeuRSs contain a large insertion domain called connective peptide 1 (CP1) within the sequence of the catalytic core. CP1 folds independently in the tertiary structure and is defined as a classic editing domain, in which the aminoacyl bond of mischarged aatRNA is hydrolyzed (post-transfer editing) to ensure the fidelity of the catalytic process. Primary sequence and tertiary structure of the CP1 hairpin of LeuRS, and structure-function relationship, overview
additional information
-
enzyme structure and tRNA binding site, the requirement of the C-terminal domain for misediting prevention is unique to LeuR, overview
additional information
-
three-dimensional LeuRS structure and sequence alignment of different eukaryal and archaeal LSD1s, overview
additional information
-
primary and tertiary structures of the LeuRS unique C-terminal domain, overview, the C-terminal extension of about 60 amino acids forms a discrete domain, which is unique among the LeuRSs and interacts with the corner of the L-shaped tRNALeu, overview
additional information
-
primary and tertiary structure, overview, the RDW peptide, a highly conserved peptide within an RDW-containing motif, is important for enzyme interactions, overview
additional information
-
homology modelling of Trypanosoma brucei LeuRS editing domain CP1 using Candida albicans LeuRS CP1 domain as the template, PDB ID 2WFG
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
lipoprotein
-
high molecular weight aminoacyl-tRNA synthetase complex contains lipid. Delipidation does not affect the size or activity of the complex, but a variety of functional and structural properties of individual synthetases in the complex are altered: sensitivity to salts plus detergents, temperature inactivation, hydrophobicity, sensitivity to protease digestion
phosphoprotein
upon glucose starvation, LARS1 is phosphorylated by Unc-51 like autophagy activating kinase 1. The phosphorylated LARS1 shows decreased leucine binding
proteolytic modification
-
processing of the mitochondrial isozyme by removing of the mitochondrial targeting presequence in the mitochondria of insect cells
additional information
-
the enzyme contains proteolytic cleavage sites at the peptide bonds between T252 and F253, E292 and A293, K327 and A328, and P368 and D369
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
structure at 2.2 A resolution of the editing domain in complex with compound AN3018, i.e.6-(ethylamino)-5-fluorobenzo[c][1,2]oxaborol-1(3H)-ol, using AMP as a surrogate for the 3' adenosine of tRNAleu. Comparison with the structure of the human enzyme
-
crystal and cocrystal structures for LeuRS, IleRS, and ValRS suggests that the CP1 domain rotates via its flexible beta-strand linkers relative to the main body along various steps in the enzymes reaction pathway. Computational analysis suggested that the end of the N-terminal beta-strand acted as a hinge. A molecular hinge might specifically direct movement of the CP1 domain relative to the main body
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crystal structure of editing domain of Escherichia coli LeuRS in both apo form and complexes with methionine and isoleucine at 2.0 A, 2.4 A, and 3.2 A resolution, hanging drop vapour diffusion method
enzyme LeuRS mutant T252A in a complex with tRNALeu and leucyl-adenylate sulphamoyl analogue (Leu-AMS), both positioned in the synthetic active site, and Leu2AA located in the editing domain, X-ray diffraction structure determination and analysis at resolution, replacement using structure PDB ID 4AQ7, modeling
LeuRS in complex with the inhibitors tested, at a resolution range between 1.9 and 2.6 A. Distinction in inhibitory activity of the compounds can be attributed to the linker and further substitutions on either the triazole or tetrazole ring
-
structure of LRS at a 2.5 A resolution, in complex with LeuAMS, an analogue of LeuAMP bound in the aminoacylation active site, and inhibitors
structure of the selenomethionine-labeled CP1 domain to 3.25 A, comparison with the structure of Candida albicans enzyme
-
LeuRS in complex with the inhibitors tested, at a resolution range between 1.9 and 2.6 A. Distinction in inhibitory activity of the compounds can be attributed to the linker and further substitutions on either the triazole or tetrazole ring
-
structures for all enzymatic states of Neisseria gonorrhoeae LeuRS during Leu-AMP formation. A cycle of conformational changes involves multiple domains, and correlates with an energetically unfavorable peptide-plane flip in the active site of the pre-transition state structure. This backbone distortion acts as a trigger, temporally compartmentalizing the first two catalytic steps
cocrystallizations with each of the tRNALeu isoacceptors are attempted. Cocrystals are obtained by the hanging-drop vapour-diffusion method, but only when the tRNALeu isoacceptor with the anticodon CAA is used. Electrophoretic analyses reveals that the crystals contain both leucyl-tRNA synthetase and tRNALeu, suggesting that they are LeuRS-tRNALeu complex crystals. A data set diffracting to 3.3 A resolution is collected from a single crystal at 100 K. The crystal belongs to the orthorhombic space group P2(1)2(1)2, with unit-cell parameters a = 118.18, b = 120.55, c = 231.13 A
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hanging-drop vapour-diffusion method using ammonium sulfate as a precipitant. The crystals belong to the rhombohedral space group R3, with unit-cell parameters a = b = 186.20, c = 91.43 A, alpha = beta = 90, gamma = 120°. The asymmetric unit contains one molecule of LeuRS, with a corresponding crystal volume per protein weight of 3.2 A3 Da(-1) and a solvent content of 60.7%. A data set diffracting to 2.2 A resolution is collected from a single crystal at -173°C. Selenomethionine-substituted protein crystals are prepared in order to solve the structure by the SAD phasing method
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hanging-drop vapour-diffusion method, resolution 2.1 A, C-terminally truncated LeuRS (amino acids 1-810), crystals belong to the Rhombohedral space group R3, with unit-cell parameters a = b = 186.23 A, c = 91.45 A, alpha = beta = 90°, gamma = 120° for the native form and a = b = 185.8 A, c = 91.19 A, alpha = beta = 90°, and gamma = 120° for the SeMet crystal
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construction of a structural model of the completely solvated leucyl-tRNA synthetase complexed with valyl-tRNALeu
crystal growth in presence of mercuric chloride, soaking of the crystals in solution containing 0.6 mM of the non-hydrolyzable substrate analogue norvaline-AMS for 1 month, or cocrystallization of enzyme and norvaline-AMS, X-ray diffraction structure determinationat 2.0-2.2 A resolution and analysis
crystal structure of leucyl-tRNA synthetase complexed with tRNALeu in the post-transfer-editing conformation, crystals of the complex are grown at 20°C by hanging drop vapour diffusion
-
crystallization of enzyme alone or in complex with leucine or leucyl-adenylate analogue, and crystallization of selenomethionine-enzyme, hanging-drop vapour-diffusion method with ammonium sulfate as precipitant, X-ray diffraction structure determination at 1.9-6 A resolution
-
hanging drop vapor diffusion method, using 0.1 M bis-Tris (pH 5.5), 0.6 M ammonium acetate, and 20% (w/v) PEG3350 at 4°C
-
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A156V
-
mutation in beta-subunit, the ratio of turnover-number to Km-value is identical to the wild-type ratio
G237D
-
mutation in beta-subunit, the ratio of turnover-number to Km-value is 1.7fold higher than the wild-type ratio
K238A
-
mutation in beta-subunit, the ratio of turnover-number to Km-value is 2.4fold higher than the wild-type ratio
K599A
-
site-directed mutagenesis, the mutation of the residue in the alpha-subunit involved in catalysis only slightly affects the enzyme activity
K599A/K600A
-
site-directed mutagenesis, the mutation of the residue in the alpha-subunit involved in catalysis only slightly affects the enzyme activity
K599A/K600A/K605A/K606A
-
site-directed mutagenesis, the mutation of the residue in the alpha-subunit involved in catalysis only slightly affects the enzyme activity
K600A
-
site-directed mutagenesis, the mutation of the residue in the alpha-subunit involved in catalysis only slightly affects the enzyme activity
K605A
-
site-directed mutagenesis, the mutation of the residue in the alpha-subunit involved in catalysis only slightly affects the enzyme activity
K605A/K606A
-
site-directed mutagenesis, the mutation of the residue in the alpha-subunit involved in catalysis only slightly affects the enzyme activity
K606A
-
site-directed mutagenesis, the mutation of the residue in the alpha-subunit involved in catalysis only slightly affects the enzyme activity
L283F
-
mutation in beta-subunit, the ratio of turnover-number to Km-value is 2fold higher than the wild-type ratio
M159A
-
mutation in beta-subunit, the ratio of turnover-number to Km-value is 80% of the wild-type value
M160N
-
mutation in beta-subunit, the ratio of turnover-number to Km-value is 2.4fold higher than the wild-type ratio
N152A
-
mutation in beta-subunit, the ratio of turnover-number to Km-value is 16% of the wild-type ratio
N163A
-
mutation in beta-subunit, the ratio of turnover-number to Km-value is 2.4fold higher than the wild-type ratio
Q234H
-
mutation in beta-subunit, the ratio of turnover-number to Km-value is identical to the wild-type ratio
Q260stop
-
mutation in beta-subunit, the ratio of turnover-number to Km-value is 0.02% of the wild-type ratio
R94A
R94A/R98A
site-directed mutagenesis, 83% reduced catalytic efficiency compared to wild-type
R94E
site-directed mutagenesis, mutating Arg94 to Glu decreases kcat/Km values to 22% of that of wild-type AaLeuRS
R94E/R98E
site-directed mutagenesis, the rate of AMP formation is decreased compared to the wild-type
R98A
site-directed mutagenesis, the mutation does not alter the catalytic efficiency
R98E
site-directed mutagenesis, the rate of AMP formation is decreased compared to the wild-type
T273R
-
no change in aminoacylation activity, but the deacylation of Ile-tRNALeu is strongly impaired. Mutant still exhibits 70% of wild-type AMP formation
V286stop
-
mutation in beta-subunit, the ratio of turnover-number to Km-value is 0.6% of the wild-type ratio
A293D
A293E
-
site-directed mutagenesis, the mutant activity is similar to the wild-type enzyme
A293F
-
54% decreased activity compared to the wild-type, more sensitive too inhibition by ATP
A293G
-
50% decreased activity, decreased editing function, stronger binding of ATP, decrease in Km for the substrates, more sensitive too inhibition by ATP
A293I
-
51% decreased activity, decreased editing function, stronger binding of ATP, decrease in Km for the substrates, more sensitive too inhibition by ATP
A293K
-
site-directed mutagenesis, the post-transfer editing activity of the isolated CP1-domain is enhanced compared to the wild-type enzyme's domain
A293R
A293Y
-
50% decreased activity, decreased editing function, stronger binding of ATP, decrease in Km for the substrates, more sensitive too inhibition by ATP
C159A
site-directed mutagenesis, structure comparison with the wild-type
C176A
site-directed mutagenesis, structure comparison with the wild-type
C179A
site-directed mutagenesis, structure comparison with the wild-type
D251W
-
site-directed mutagenesis, editing site mutant, the substrate specificity and charging fidelity is retained
D342A
site-directed mutagenesis, the mutant shows altered deacylation activity with amino acids norvaline, isoleucine, and leucine compared to the wild-type enzyme, overview
D345A
DELTA788-798
-
partial deletion of the C-terminal domain peptide linker shows that as the length of the peptide linker decreases, aminoacylation activity decreases. This mutant shows almost no aminoacylation activity. Mutant shows reduced deacylation activity against mischarged Ile-tRNALeu
DELTA790-798
-
partial deletion of the C-terminal domain peptide linker shows that as the length of the peptide linker decreases, aminoacylation activity decreases. Mutant shows reduced deacylation activity against mischarged Ile-tRNALeu
DELTA792-798
-
partial deletion of the C-terminal domain peptide linker shows that as the length of the peptide linker decreases, aminoacylation activity decreases. Mutant retains significant deacylation activity against mischarged Ile-tRNALeu
DELTA793
-
single-site deletion at the more flexible end of the peptide linker: no significant change in aminoacylation activity
DELTA794
-
single-site deletion at the more flexible end of the peptide linker: no significant change in aminoacylation activity
DELTA794-798
-
partial deletion of the C-terminal domain peptide linker shows that as the length of the peptide linker decreases, aminoacylation activity decreases. Mutant retains significant deacylation activity against mischarged Ile-tRNALeu
DELTA795
-
single-site deletion at the more flexible end of the peptide linker: no significant change in aminoacylation activity
DELTA795-796
-
two-site deletion at the more flexible end of the peptide linker: no significant change in aminoacylation activity
DELTA795-798
-
partial deletion of the C-terminal domain peptide linker shows that as the length of the peptide linker decreases, aminoacylation activity decreases. Mutant retains significant deacylation activity against mischarged Ile-tRNALeu
DELTA796
-
single-site deletion at the more flexible end of the peptide linker: no significant change in aminoacylation activity
DELTA796-798
DELTA797
-
single-site deletion at the more flexible end of the peptide linker: no significant change in aminoacylation activity
DELTA797-798
-
two-site deletion at the more flexible end of the peptide linker: mutant exhibits lower aminoacylation activity compared to wild-type
E184A
the mutant performs the activities of amino acid activation, aminoacylation and deacylation of mischarged tRNAs as well as the native enzyme
E184R
the mutant performs the activities of amino acid activation, aminoacylation and deacylation of mischarged tRNAs as well as the native enzyme. The substitution specifically inhibits tRNA-dependent pre-transfer editing
E184R/T252R
the mutant performs the activities of amino acid activation, aminoacylation and deacylation of mischarged tRNAs as well as the native enzyme
E292A
-
unaltered specific activity in amino acid activation reaction, 61% reduced aminoacylation activity compared to the wild-type
E292D
-
unaltered specific activity in amino acid activation reaction, 53% reduced aminoacylation activity compared to the wild-type
E292F
-
unaltered specific activity in amino acid activation reaction, 60% reduced aminoacylation activity compared to the wild-type
E292K
-
unaltered specific activity in amino acid activation reaction, 85% reduced aminoacylation activity compared to the wild-type
E292Q
-
unaltered specific activity in amino acid activation reaction, 54% reduced aminoacylation activity compared to the wild-type
E292S
-
unaltered specific activity in amino acid activation reaction, 66% reduced aminoacylation activity compared to the wild-type
E797GGG
-
mutant shows no altered aminoacylation activity compared to wild-type
E797PPP
-
mutant shows no altered aminoacylation activity compared to wild-type
G225P
-
abolishes tRNA leucylation due to a defect in leucine activation, decrease in deacylation of Ile-tRNALeu
G229P
-
increased aminoacylation activity compared to the wild-type, mutant deacylates Ile-tRNALeu similar to wild-type
G229P/T252A
-
double mutant rescues leucylation activity to levels comparable to wild-type and retains deacylation activity of LeutRNALeu that is characteristic of the T252A mutation
G407P
-
aminoacylates tRNALeu and decylates Ile-tRNALeu as well as wild-type
G409P
-
increased aminoacylation activity compared to the wild-type, mutant deacylates Ile-tRNALeu similar to wild-type
K671A
site-directed mutagenesis, the mutation does no affect the catalytic efificiency
K809A
-
site-directed mutagenesis, the mutant shows decreased activity compared to the wild-typ enzyme
K846A
-
site-directed mutagenesis, the mutant shows increased activity compared to the wild-typ enzyme
K846A/K853A
-
site-directed mutagenesis, the mutant shows decreased activity compared to the wild-typ enzyme
K846E
-
site-directed mutagenesis, the mutant shows similar activity compared to the wild-typ enzyme
K846E/K853E
-
site-directed mutagenesis, the mutant shows decreased activity compared to the wild-typ enzyme
K853A
-
site-directed mutagenesis, the mutant shows unaltered activity compared to the wild-typ enzyme
K853E
-
site-directed mutagenesis, the mutant shows increased activity compared to the wild-typ enzyme
L570F
-
the mutation leads to altered catalytic efficiency and perturbations to the discrimination of leucine and isoleucine and affects tRNA recognition and aminoacylation, it shows a catalytic turnover for isoleucine decreased by a factor of 2, L570F has an 11fold higher Km for leucine compared to the wild-type enzyme, the activity is reduceDdcompared to the wild-type enzyme
L570K
-
the mutation leads to altered catalytic efficiency and perturbations to the discrimination of leucine and isoleucine and affects tRNA recognition and aminoacylation, it shows a catalytic turnover for isoleucine decreased by a factor of 2, L570F has an 11fold higher Km for leucine compared to the wild-type enzyme, the activity is reduced compared to the wild-type enzyme
L570R
-
the mutation leads to altered catalytic efficiency and perturbations to the discrimination of leucine and isoleucine and affects tRNA recognition and aminoacylation, it shows a catalytic turnover for isoleucine decreased by a factor of 2, L570R has a 4fold stronger binding affinity for leucine compared to the wild-type enzyme, the activity is reduce compared to the wild-type enzyme
L854A
-
site-directed mutagenesis, the mutant shows increased activity compared to the wild-typ enzyme
L855A
-
site-directed mutagenesis, the mutant shows decreased activity compared to the wild-typ enzyme
M336A
-
site-directed mutagenesis, editing site mutant, the mutant shows a small increase in leucine editing activity
M336F/T252A
-
site-directed mutagenesis, editing site mutant, the T252A mutation uncouples specificity, M336F/T252A double LeuRS mutant exhibited only slightly increased leucylation activity relative to the T252A single mutation
N807A
-
site-directed mutagenesis, the mutant shows similar activity compared to the wild-typ enzyme
N807A/N856A
-
site-directed mutagenesis, the mutant shows similar activity compared to the wild-typ enzyme
N856A
-
site-directed mutagenesis, the mutant shows increased activity compared to the wild-typ enzyme
Q805A
-
site-directed mutagenesis, the mutant shows decreased activity compared to the wild-typ enzyme
Q805A/N807A
-
site-directed mutagenesis, the mutant shows decreased activity compared to the wild-typ enzyme
Q805A/N807A/N856A
-
site-directed mutagenesis, the mutant shows decreased activity compared to the wild-typ enzyme
R185E
the mutation significantly enhances tRNA-dependent pre-transfer editing activity
R249F
-
site-directed mutagenesis, editing site mutant, editing activity of Leu-tRNALeu is decreased
R249F/T252A
-
site-directed mutagenesis, editing site mutant, the T252A mutation uncouples specificity
R249T
-
site-directed mutagenesis, editing site mutant, the mutant shows increased activity with tRNALeu, but even higher activity with tRNAIle compared to the wild-type enzyme
R249T/D251W
-
site-directed mutagenesis, editing site mutant, the mutant shows decreased hydrolysis of mischarged Ile-tRNALeu compared to the wild type enzyme
R286E
the mutation significantly enhances tRNA-dependent pre-transfer editing activity
R344A
site-directed mutagenesis, the mutant shows altered deacylation activity with amino acids norvaline, isoleucine, and leucine compared to the wild-type enzyme, overview
R668A
site-directed mutagenesis, the mutant shows 77% reduced catalytic efficiency compared to wild-type, the rate of AMP formation is decreased compared to the wild-type
R668A/R672A
site-directed mutagenesis, the mutant shows 93.6% reduced catalytic efficiency compared to wild-type, the rate of AMP formation is decreased compared to the wild-type
R668E
site-directed mutagenesis, the mutant shows 95% reduced catalytic efficiency compared to wild-type, the rate of AMP formation is decreased compared to the wild-type
R668E/R672E
site-directed mutagenesis, the mutant shows 98.6% reduced catalytic efficiency compared to wild-type. But the almost inactive mutant exhibits intact Leu activation activity comparable with the wild-type enzyme
R672A
site-directed mutagenesis, the rate of AMP formation is decreased compared to the wild-type
R672E
site-directed mutagenesis, the rate of AMP formation is decreased compared to the wild-type
R811A
-
site-directed mutagenesis, the mutant shows decreased activity compared to the wild-typ enzyme
T247A/T248A
-
533fold decrease in the ratio of turnover number to Km-value compared to wild-type ratio
T247S/T248S
-
77fold decrease in the ratio of turnover number to Km-value compared to wild-type ratio
T247V
T247V/T248V
T248A
site-directed mutagenesis, the mutant shows altered deacylation activity with amino acids norvaline, isoleucine, and leucine compared to the wild-type enzyme, overview
T248V
T252A
T252D
-
mutation results in isoleucylation of tRNALeu, editing activity is impaired, ATP hydrolysis in presence of norvaline is 27% of the wild-type value, ATP hydrolysis in presence of leucine is 98% of the wild-type value
T252E
T252F
-
impaired proofreading mechanism, increase rate of misaminoacylation with isoleucine and valine
T252G
-
the mutant enzyme, like the native enzyme, does not mischarge tRNALeu with isoleucine, ATP hydrolysis in presence of norvaline is 2.1fold higher than wild-type value, ATP hydrolysis in presence of leucine is 60% of the wild-type value
T252L
-
impaired proofreading mechanism, increase rate of misaminoacylation with isoleucine and valine
T252R
the mutant performs the activities of amino acid activation, aminoacylation and deacylation of mischarged tRNAs as well as the native enzyme
T252S
-
the ratio of turnover-number to KM-value for L-leucine in aminoacylation is 60% of the wild-type ratio, the ratio of turnover-number to KM-value for tRNALeu in aminoacylation is 80% of the wild-type ratio. The ratio of turnover-number to Km value for Leu-tRNALeu(UAA) is 7.5fold higher than the wild-type value, the ratio of turnover-number to Km value for Ile-tRNALeu(UAA) is 1.6fold lower than the wild-type value
T252V
-
the ratio of turnover-number to KM-value for L-leucine in aminoacylation is identical to wild-type ratio, the ratio of turnover-number to KM-value for tRNALeu in aminoacylation is 90% of the wild-type ratio. The ratio of turnover-number to Km value for Leu-tRNALeu(UAA) is 1.75fold higher than the wild-type value, the ratio of turnover-number to Km value for Ile-tRNALeu(UAA) is 13.3fold higher than the wild-type value
T252Y
T272R
-
no change in aminoacylation activity, but the deacylation of Ile-tRNALeu is strongly impaired. Mutant still exhibits 45% of wild-type AMP formation
V338A
-
site-directed mutagenesis, editing site mutant, it shows increased post-transfer editing activity of Leu-tRNALeu compared to the wild-type enzyme
V338D
-
site-directed mutagenesis, editing site mutant, the mutant shows reduced post-transfer editing activity compared to the wild-type enzyme
V338E
-
site-directed mutagenesis, editing site mutant, the mutant shows reduced post-transfer editing activity compared to the wild-type enzyme
V338F
-
site-directed mutagenesis, editing site mutant, single introduction of the bulky phenylalanine residue nearly abolished post-transfer editing activity and facilitated mischarging of both isoleucine and valine to tRNALeu, 3000fold reduced activity
V338F/T252A
-
site-directed mutagenesis, editing site mutant, the T252A mutation uncouples specificity
V338L
-
site-directed mutagenesis, editing site mutant, the mutant shows reduced post-transfer editing activity compared to the wild-type enzyme
D173A
-
site-directed mutagenesis, mutant kinetics compared to the wild-type enzyme, overview
D444A
D588A
-
kcat/Km: 0.57 (ATP), 0.37 (Leu), mutant displays lower amino acid activation and aminoacylation activities than wild-type
D603A
-
kcat/Km: 0.91 (ATP), 0.94 (Leu), similar activity compared to wild-type
DELTA581-617
-
deletion of the CP2 domain, an insertion domain called connective peptide 2, of Giardia lamblia LeuRS shows that the CP2 domain is indispensable for amino acid activation, post-transfer editing and contributes to LeuRS-tRNALeu binding affinity. CP2 domain of Pyrococcus horikoshii LeuRS but not that of Escherichia coli LeuRS can partially restore amino acid activation and post-transfer editing functions suggesting that the functions of the CP2 domain are dependent on its location in the primary sequence of LeuRS
E165A
-
site-directed mutagenesis, mutant kinetics compared to the wild-type enzyme, overview
E167A
-
site-directed mutagenesis, the mutant shows defects in leucine activation, mutant kinetics compared to the wild-type enzyme, overview
K139A
-
site-directed mutagenesis, mutant kinetics compared to the wild-type enzyme, overview
K141A
-
site-directed mutagenesis, mutant kinetics compared to the wild-type enzyme, overview
K142A
-
site-directed mutagenesis, mutant kinetics compared to the wild-type enzyme, overview
K144A
-
site-directed mutagenesis, mutant kinetics compared to the wild-type enzyme, overview
K148A
-
site-directed mutagenesis, mutant kinetics compared to the wild-type enzyme, overview
K152A
-
site-directed mutagenesis, the mutant shows defects in leucine activation, mutant kinetics compared to the wild-type enzyme, overview
K166A
-
site-directed mutagenesis, mutant kinetics compared to the wild-type enzyme, overview
K170A
-
site-directed mutagenesis, mutant kinetics compared to the wild-type enzyme, overview
K587A
-
kcat/Km: 0.43 (ATP), 0.42 (Leu), mutant displays lower amino acid activation and aminoacylation activities than wild-type
K606A
-
mutant shows a complete loss of amino acid activation, aminoacylation and post-transfer editing activities
K606D
-
kcat/Km: 0.86 (ATP), 0.83 (Leu), similar leucine activation and post-transfer editing activities compared to wild-type
K606E
-
kcat/Km: 0.90 (ATP), 0.99 (Leu), no difference in leucine activation and post-transfer editing activities compared to wild-type
K606L
-
kcat/Km: 0.85 (ATP), 0.98 (Leu), similar leucine activation and post-transfer editing activities compared to wild-type
K606R
-
kcat/Km: 0.98 (ATP), 0.99 (Leu), no difference in leucine activation and post-transfer editing activities compared to wild-type
Q154A
-
site-directed mutagenesis, the mutant shows defects in leucine activation, mutant kinetics compared to the wild-type enzyme, overview
R338A
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
S153A
-
site-directed mutagenesis, mutant kinetics compared to the wild-type enzyme, overview
T341A
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
T341R
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
W155A
-
site-directed mutagenesis, mutant kinetics compared to the wild-type enzyme, overview
W586A
-
mutant shows a complete loss of amino acid activation, aminoacylation and post-transfer editing activities
Y581A
-
mutant shows a complete loss of amino acid activation, aminoacylation and post-transfer editing activities
Y581E
-
mutant is unable to activate leucine by the ATP-diphosphate exchange assay, and mutant has no post-transfer editing activity
Y581F
-
mutant shows some but significantly reduced leucine activation activity its post-transfer editing activity is similar to wild-type
Y581K
-
mutant is unable to activate leucine by the ATP-diphosphate exchange assay, and mutant has no post-transfer editing activity
Y581S
-
mutant is unable to activate leucine by the ATP-diphosphate exchange assay, and mutant has no post-transfer editing activity
A3243G
-
respiratory chain defects in A3243G mutant cells is suppressed by overexpressing human mitochondrial leucyl-tRNA synthetase. The rates of oxygen consumption in suppressed cells are directly proportional to the levels of leucyl-tRNA synthetase. 15fold higher levels of leucyl-tRNA synthetase results in wild-type respiratory chain function. The suppressed cells have increased steady-state levels of tRNA(Leu(UUR)) and up to 3fold higher steady-state levels of mitochondrial translation products, but do not have rates of protein synthesis above those in parental mutant cells
A525S
site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
C527E
site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
D250A
site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
D250E
site-directed mutagenesis, the mutant shows slightly altered kinetics and slightly reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
D250N
site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
D399A
D399K
-
mutant is resitant to inhibitor 5-fluoro-2,1-benzoxaborol-1(3H)-ol but more sensitive to norvaline inhibition
D528R
site-directed mutagenesis, the mutant shows altered kinetics, reduced catalytic efficiency in the aminoacylation reaction, and 85% reduced amino acid activation activity compared to the wild-type enzyme
F50A/Y52A
site-directed mutagenesis, the leucine-binding deficient LRS mutant also activates Vps34, but to a lesser degree and in a leucine-independent manner
G245A
site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
G245D
site-directed mutagenesis, the mutant shows altered kinetics and 50% reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
G245R
site-directed mutagenesis, the mutant shows altered kinetics and 50% reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
K600F
-
the mutation leads to altered catalytic efficiency and perturbations to the discrimination of leucine and isoleucine and affects tRNA recognition and aminoacylation, the mutant demonstrates a 9fold decrease in its ability to distinguish between leucine and isoleucine effectively, the activity is reduced compared to the wild-type enzyme
K600L
-
the mutation leads to altered catalytic efficiency and perturbations to the discrimination of leucine and isoleucine and affects tRNA recognition and aminoacylation, the mutant demonstrates an 11fold increase in its ability to distinguish between leucine and isoleucine effectively, the activity is reduced compared to the wild-type enzyme
K600R
-
the mutation leads to altered catalytic efficiency and perturbations to the discrimination of leucine and isoleucine and affects tRNA recognition and aminoacylation, the mutant shows a slight decrease in activity compared to the wild-type enzyme
P242E
site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
P247A
site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
Q529A
site-directed mutagenesis, the mutant shows altered kinetics, reduced catalytic efficiency in the aminoacylation reaction, and 70% reduced amino acid activation activity compared to the wild-type enzyme
R236D
site-directed mutagenesis, the mutant shows altered kinetics, reduced catalytic efficiency in the aminoacylation reaction, and 30% reduced amino acid activation activity compared to the wild-type enzyme
R517D
site-directed mutagenesis, the mutant shows altered kinetics, reduced catalytic efficiency in the aminoacylation reaction, and 90% reduced amino acid activation activity compared to the wild-type enzyme
R766A
site-directed mutagenesis, the mutation decreases the kcat/Km value to less than 10% that of the wild-type enzyme hcLeuRS
S519G
site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
T298A
activity similar to wild-type, mutation maintains Ile-tRNALeu deacylation activity
T298Y
mutation uncouples specificity in the editing active site and mutant hydrolyzes Leu-tRNALeu
V523I
site-directed mutagenesis, the mutant shows altered kinetics and reduced catalytic efficiency in the aminoacylation reaction compared to the wild-type enzyme
W530A
site-directed mutagenesis, the mutant shows altered kinetics, reduced catalytic efficiency in the aminoacylation reaction, and 50% reduced amino acid activation activity compared to the wild-type enzyme
Y240A
site-directed mutagenesis, the mutant shows altered kinetics, reduced catalytic efficiency in the aminoacylation reaction, and 50% reduced amino acid activation activity compared to the wild-type enzyme
Y531A
site-directed mutagenesis, the mutant shows altered kinetics, reduced catalytic efficiency in the aminoacylation reaction, and 50% reduced amino acid activation activity compared to the wild-type enzyme
Y534A
site-directed mutagenesis, the mutant shows altered kinetics, reduced catalytic efficiency in the aminoacylation reaction, and 60% reduced amino acid activation activity compared to the wild-type enzyme
L949A
-
the mutant shows 9.5% activity compared to the wild type enzyme
L949K
-
the mutant shows 2.6% activity compared to the wild type enzyme
L964A
-
the mutant shows 85% activity compared to the wild type enzyme
L964K
-
the mutant shows 8.6% activity compared to the wild type enzyme
Q915A
-
the mutant shows 99% activity compared to the wild type enzyme
Q915K
-
the mutant shows 54% activity compared to the wild type enzyme
R921A
-
the mutant shows 37% activity compared to the wild type enzyme
R921K
-
the mutant shows 83% activity compared to the wild type enzyme
V910A
-
the mutant shows 90% activity compared to the wild type enzyme
V910P
-
the mutant shows 3.7% activity compared to the wild type enzyme
V910W
-
the mutant shows 93% activity compared to the wild type enzyme
Q915A
-
the mutant shows 99% activity compared to the wild type enzyme
-
Q915K
-
the mutant shows 54% activity compared to the wild type enzyme
-
V910A
-
the mutant shows 90% activity compared to the wild type enzyme
-
V910P
-
the mutant shows 3.7% activity compared to the wild type enzyme
-
V910W
-
the mutant shows 93% activity compared to the wild type enzyme
-
D121A
-
site-directed mutagenesis, mutant steady-state leucine activation kinetics compared to the wild-type enzyme, overview
D332A
D98A
-
site-directed mutagenesis, mutant steady-state leucine activation kinetics compared to the wild-type enzyme, overview
E113A
-
site-directed mutagenesis, mutant steady-state leucine activation kinetics compared to the wild-type enzyme, overview
E114A
-
site-directed mutagenesis, mutant steady-state leucine activation kinetics compared to the wild-type enzyme, overview
F119A
-
site-directed mutagenesis, mutant steady-state leucine activation kinetics compared to the wild-type enzyme, overview
I104A
-
site-directed mutagenesis, mutant steady-state leucine activation kinetics compared to the wild-type enzyme, overview
I115A
-
site-directed mutagenesis, mutant steady-state leucine activation kinetics compared to the wild-type enzyme, overview
K100A
-
site-directed mutagenesis, mutant steady-state leucine activation kinetics compared to the wild-type enzyme, overview
K100A/Y105A
-
site-directed mutagenesis, mutant steady-state leucine activation kinetics compared to the wild-type enzyme, overview
K100A/Y109A
-
site-directed mutagenesis, mutant steady-state leucine activation kinetics compared to the wild-type enzyme, overview
K692A
site-directed mutagenesis, the mutation has no effect on tRNA charging activity
K696A
site-directed mutagenesis, the mutant shows a highly reduced kcat value compared to wild-type, while the Km value is 3fold increased
K699A
site-directed mutagenesis, the mutation has no effect on tRNA charging activity
N96A
-
site-directed mutagenesis, mutant steady-state leucine activation kinetics compared to the wild-type enzyme, overview
R106A
-
site-directed mutagenesis, mutant steady-state leucine activation kinetics compared to the wild-type enzyme, overview
R698A
site-directed mutagenesis, the mutation has no effect on tRNA charging activity
R703A
site-directed mutagenesis, kcat of mutant PhLeuRSR703A is much lower than that of wild-type PhLeuRS
R97A
-
site-directed mutagenesis, mutant steady-state leucine activation kinetics compared to the wild-type enzyme, overview
T101A
-
site-directed mutagenesis, mutant steady-state leucine activation kinetics compared to the wild-type enzyme, overview
T118A
-
site-directed mutagenesis, mutant steady-state leucine activation kinetics compared to the wild-type enzyme, overview
V108A
-
site-directed mutagenesis, mutant steady-state leucine activation kinetics compared to the wild-type enzyme, overview
W103A
-
site-directed mutagenesis, mutant steady-state leucine activation kinetics compared to the wild-type enzyme, overview
Y105A
-
site-directed mutagenesis, mutant steady-state leucine activation kinetics compared to the wild-type enzyme, overview
Y109A
-
site-directed mutagenesis, mutant steady-state leucine activation kinetics compared to the wild-type enzyme, overview
K692A
Pyrococcus horikoshii ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3
-
site-directed mutagenesis, the mutation has no effect on tRNA charging activity
-
K696A
Pyrococcus horikoshii ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3
-
site-directed mutagenesis, the mutant shows a highly reduced kcat value compared to wild-type, while the Km value is 3fold increased
-
K699A
Pyrococcus horikoshii ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3
-
site-directed mutagenesis, the mutation has no effect on tRNA charging activity
-
R698A
Pyrococcus horikoshii ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3
-
site-directed mutagenesis, the mutation has no effect on tRNA charging activity
-
R703A
Pyrococcus horikoshii ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3
-
site-directed mutagenesis, kcat of mutant PhLeuRSR703A is much lower than that of wild-type PhLeuRS
-
D357A
-
site-directed mutagenesis, the mutant shows reduced activity and abolished editing activity and misaminoacylated isoleucine to tRNALeu compared to the wild-type enzyme
D418R
mutant is significantly resistant to inhibitor AN-2690. Mutant aminoacylation of yctRNALeu is not different from wild-type ycLeuRS. Growth rate is similar to wild-type. Growth rate is moderately inhibited in medium containing a large excess of norvaline and reduced leucine
D419A
DELTA270-530
deletion of the CP1 domain shows that the mutant is not able to rescue LeuRS knock-out strain
DELTA314-319
deletion of the T-rich region shows that the mutant is able to rescue LeuRS knock-out strain with a grwoth rate similar to wild-type
DELTA819-828
-
deletion of the C-terminal domain peptide linker stimulates aminoacylation and editing activity shows that as the length of the peptide linker decreases, aminoacylation activity decreases. Mutant retains significant deacylation activity against mischarged Ile-tRNALeu
K404Y
mutant is significantly resistant to inhibitor AN-2690. Mutant aminoacylation of yctRNALeu is not different from wild-type ycLeuRS. Growth rate is similar to wild-type. Growth rate is moderately inhibited in medium containing a large excess of norvaline and reduced leucine
R265A
-
site-directed mutagenesis, the mutant shows reduced activity and abolished post-transfer editing activity compared to the wild-type enzyme
R449E
-
site-directed mutagenesis, mutation within the RDW peptide, no complementation of the null mutant strain QBY320
R449K
-
site-directed mutagenesis, mutation within the RDW peptide, no complementation of the null mutant strain QBY320, 30fold reduced activity compared to the wild-type enzyme
R451E
-
site-directed mutagenesis, mutation within the RDW peptide, no complementation of the null mutant strain QBY320
R451K
-
site-directed mutagenesis, mutation within the RDW peptide, complementation of the null mutant strain QBY320, 11fold reduced activity compared to the wild-type enzyme
S416D
mutant is significantly resistant to inhibitor AN-2690. Mutant aminoacylation of yctRNALeu is not different from wild-type ycLeuRS. Growth rate is similar to wild-type. Growth rate is moderately inhibited in medium containing a large excess of norvaline and reduced leucine
T263V/T264V
-
site-directed mutagenesis, the mutant shows reduced activity and decreased post-transfer editing activity compared to the wild-type enzyme
T31E
mutant is significantly resistant to inhibitor AN-2690. Mutant aminoacylation of yctRNALeu is not different from wild-type ycLeuRS. Growth rate is similar to wild-type. Mutant T319A shows mischarging capacity with Ile. Growth rate is severly inhibited in medium containing a large excess of norvaline and reduced leucine
T347A
mutant is inhibited by AN-2690. Mutant aminoacylation of yctRNALeu is not different from wild-type ycLeuRS. Growth rate is similar to wild-type. Growth rate is moderately inhibited in medium containing a large excess of norvaline and reduced leucine
T410A
mutant is inhibited by AN-2690. Mutant aminoacylation of yctRNALeu is not different from wild-type ycLeuRS. Growth rate is similar to wild-type. Growth rate is moderately inhibited in medium containing a large excess of norvaline and reduced leucine
W445F
-
site-directed mutagenesis, mutation within the RDW peptide, no complementation of the null mutant strain QBY320
W445H
-
site-directed mutagenesis, mutation within the RDW peptide, no complementation of the null mutant strain QBY320
W445K
-
site-directed mutagenesis, mutation within the RDW peptide, no complementation of the null mutant strain QBY320
W445Y
-
site-directed mutagenesis, mutation within the RDW peptide, weak complementation of the null mutant strain QBY320, 30fold reduced activity compared to the wild-type enzyme
D347A
mutation of the highly conserved Asp residue, located in the CP1 domain, is responsible for editing mechanism, slightly reduced activity with L-leucine, mutant mischarges tRNALeu with isoleucine
K452A
site-directed mutagenesis, the mutation has only a minimal effect on aminoacylation activity, the Km values is not significantly altered compared to wild-type
K452E
site-directed mutagenesis, the mutation has only a minimal effect on aminoacylation activity, the Km values is not significantly altered compared to wild-type
K598A
-
the mutation simultaneously reduces the tRNA-binding strength and aminoacylation and editing capacities of the enzyme's leucine-specific domain
R456A
site-directed mutagenesis, 75% reduced catalytic efficiency compared to wild-type, the Km values is not significantly altered
R456E
site-directed mutagenesis, 79% reduced catalytic efficiency compared to wild-type, the Km values is not significantly altered
K452A
[Mycoplasma] mobile ATCC 43663 / 163K / NCTC 11711
-
site-directed mutagenesis, the mutation has only a minimal effect on aminoacylation activity, the Km values is not significantly altered compared to wild-type
-
K452E
[Mycoplasma] mobile ATCC 43663 / 163K / NCTC 11711
-
site-directed mutagenesis, the mutation has only a minimal effect on aminoacylation activity, the Km values is not significantly altered compared to wild-type
-
R456A
[Mycoplasma] mobile ATCC 43663 / 163K / NCTC 11711
-
site-directed mutagenesis, 75% reduced catalytic efficiency compared to wild-type, the Km values is not significantly altered
-
R456E
[Mycoplasma] mobile ATCC 43663 / 163K / NCTC 11711
-
site-directed mutagenesis, 79% reduced catalytic efficiency compared to wild-type, the Km values is not significantly altered
-
additional information
R94A
-
mutation in beta-subunit, the ratio of turnover-number to Km-value is 40% of the wild-type ratio
R94A
site-directed mutagenesis, mutating Arg94 to Ala decreases kcat/Km values to 34% of that of wild-type AaLeuRS
A293D
-
81% decreased activity, highly decreased editing function, very strong binding of ATP, high decrease in Km for the substrates, more sensitive too inhibition by ATP, increased heat lability compared to the wild-type
A293D
-
site-directed mutagenesis, the mutant activity is similar to the wild-type enzyme
A293R
-
30% decreased activity, decreased editing function, stronger binding of ATP, decrease in Km for the substrates
A293R
-
site-directed mutagenesis, the post-transfer editing activity of the isolated CP1-domain is enhanced compared to the wild-type enzyme's domain
D345A
-
mutation of the highly conserved Asp residue, located in the CP1 domain, is responsible for editing mechanism, slightly reduced activity with L-leucine, mutant mischarges tRNALeu with isoleucine
D345A
-
site-directed mutagenesis, the mutation in the isolated CP1-domain abolishes hydrolytic post-transfer editing activity
D345A
site-directed mutagenesis, the mutant shows altered deacylation activity with amino acids norvaline, isoleucine, and leucine compared to the wild-type enzyme, overview
DELTA796-798
-
partial deletion of the C-terminal domain peptide linker shows that as the length of the peptide linker decreases, aminoacylation activity decreases. Mutant retains significant deacylation activity against mischarged Ile-tRNALeu
DELTA796-798
-
two-site deletion at the more flexible end of the peptide linker: mutant exhibits lower aminoacylation activity compared to wild-type
T247V
-
8fold decrease in the ratio of turnover number to Km-value compared to wild-type ratio
T247V
-
site-directed mutagenesis, hydrolysis of Ile-tRNALeu is completely abolished
T247V/T248V
-
fold decrease in the ratio of turnover number to Km-value compared to wild-type ratio
T247V/T248V
-
site-directed mutagenesis, the double mutation abolishes post-transfer editing activity
T248V
-
6fold decrease in the ratio of turnover number to Km-value compared to wild-type ratio
T248V
-
site-directed mutagenesis, hydrolysis of Ile-tRNALeu is completely abolished
T252A
-
decreased activity with L-leucine, mutant shows altered editing specificity, it edits correctly formed leucyl-tRNALeu
T252A
-
the ratio of turnover-number to KM-value for L-leucine in aminoacylation is 5% of the wild-type ratio, the ratio of turnover-number to KM-value for tRNALeu in aminoacylation is 10% of the wild-type ratio. The ratio of turnover-number to Km value for Leu-tRNALeu(UAA) is 25fold higher than the wild-type value, the ratio of turnover-number to Km value for Ile-tRNALeu(UAA) is 1.25fold higher than the wild-type value
T252A
-
site-directed mutagenesis, the mutation uncouples specificity and shows a 24-fold increase in hydrolytic activity compared to the wild-type enzyme, introduction of the large aromatic residue at Arg249 or Val338 rescued leucylation activity of the T252A mutation
T252A
-
site-directed mutagenesis, the mutation in the full-length LeuRS uncouples specificity and hydrolyzes correctly charged LeutRNALeu
T252A
site-directed mutagenesis, the mutant shows altered deacylation activity with amino acids norvaline, isoleucine, and leucine compared to the wild-type enzyme, conformational changes associated with the binding of post-transfer editing analogues in the editing site of T252A LeuRS, overview
T252E
-
mutation results in isoleucylation of tRNALeu, editing activity is impaired, ATP hydrolysis in presence of norvaline is 18% of the wild-type value, ATP hydrolysis in presence of leucine is 86% of the wild-type value
T252Y
-
impaired proofreading mechanism, increase rate of misaminoacylation with isoleucine and valine, effective aminoacylation of tRNALeu with allylglycine, homopropargylglycine, 2-butynylalanine, norvaline, and norisoleucine
T252Y
-
site-directed mutagenesis, the mutation occupies the amino acid binding pocket and blocks the binding of substrate to abolish editing activity
T252Y
-
mutant is unable to proofread amino acids with unbranched side chains, and enables insertion of a variety of noncanonical amino acids into recombinant proteins in place of leucine
D444A
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
D444A
-
site-directed mutagenesis, mutant kinetics compared to the wild-type enzyme, overview
D399A
40fold increase in Km for leucine activation. Mutation eliminates Ile-tRNALeu deacylation activity
D399A
-
site-directed mutagenesis, tRNA selectivity compared to the wild-type enzyme
D332A
-
unlike the wild-type enzyme the mutant enzyme synthesizes the incorrect product Ile-tRNALeu, unlike the wild-type enzyme, the mutant enzyme cannot deacylate Ile-tRNALeu
D419A
-
mutation of the highly conserved Asp residue, located in the CP1 domain, is responsible for editing mechanism, slightly reduced activity with L-leucine, mutant mischarges tRNALeu with isoleucine
D419A
mutant is significantly resistant to inhibitor AN-2690. Mutant aminoacylation of yctRNALeu is not different from wild-type ycLeuRS. Growth rate is similar to wild-type. Mutant D419A shows mischarging capacity with Ile. Growth rate is severly inhibited in medium containing a large excess of norvaline and reduced leucine
additional information
-
deletion of the last 36 residues of the alpha-subunit is deleterious for tRNA charging, resulting in an inactive mutant, the monomeric mutants containing the alpha-subunit have activities comparable to the wild-type enzyme, while the heterodimeric enzymes show very low activity
additional information
-
the freestanding LeuRS editing domain can edit this precursor in contrast to IleRS and ValRS editing domains, overview, design and preparation of minihelixLIV, overview
additional information
-
construction of diverse truncation mutants, ATP-diphosphate-exchange and aminoacylation activities, and ability to charge minihelixLeu of alpha and beta subunit mutants, overview
additional information
-
a mutation in the gene, leuS1, increases the transcription and expression of the ilv-leu operon, permitting monitoring of leuS alleles
additional information
-
using a Chinese hamster ovary cell line containing a temperature-sensitive mutation in leucyl-tRNA synthetase which is active at 34 °C but defective at 39.5 °C, it is shown that shifting the cells to the latter temperature mimics the effects of amino acid starvation on protein synthesis. Leucine deprivation markedly inhibits mTORC1 signaling in these cells, but shifting the cells to the nonpermissive temperature for the synthetase does not. These data indicate that uncharged tRNALeu does not switch off mTORC1 signaling and suggest that mTORC1 is controlled by a distinct pathway that senses the availability of amino acids
additional information
-
overexpression of the alpha and beta subunits of the Aquifex aeolicus enzyme and the C- and N-terminal parts of the Escherichia coli enzyme in Escherichia coli as monomeric and dimeric mutants, also mixed between the species, the heterodimeric mutants and the monomeric mutants containing the N-terminal-subpart of the enzyme show very low activity
additional information
-
construction of an enzyme mutant with a duplication of the peptide fragment from Met238 to Pro368 within the CP1 domain which shows an activity reduced by 59% compared to the wild-type enzyme, and catalyzes the mischarging of tRNALeu by methionine or isoleucine due to impaired ability to edit incorrect products
additional information
-
construction of several CP1 domain mutants by introduction of restriction endonuclease sites into gene leuS
additional information
-
deletion of the unique inserted leucine-specific domain of LeuRS primarily impacts kcat, chimeric LeuRS and ValRS mutants restore limited aminoacylation actiVity, overview
additional information
-
isolated LeuRS CP1 domain requires idiosyncratic adaptations to confer editing activity independent of the full-length enzyme, the beta-strands, which link the CP1 domain to the aminoacylation core of LeuRS, are required for editing of mischarged tRNALeu, hydrolytic activity is also enhanced by inclusion of short flexible peptides, called hinges, at the end of both LeuRS beta-strands, overview
additional information
-
deletions of the C terminus differentially impact the two functions of the enzyme in splicing and aminoacylation in vivo, overview, a five-amino acid C-terminal deletion of LeuRS, which does not complement a null strain, can form a ternary complex with the bI4 intron and its maturase splicing partner, however, the complex fails to stimulate splicing activity, deletion of the C-terminal domain of LeuRS abolishes aminoacylation of tRNALeu and also amino acid editing of mischarged tRNA molecules, overview
additional information
C159A, C176A and C179A disassociate from Zn2+ much more readily than wild-type LeuRS, the wild-type LeuRS binds more tightly to Zn2+ than do C159A, C176A or C179A
additional information
-
C159A, C176A and C179A disassociate from Zn2+ much more readily than wild-type LeuRS, the wild-type LeuRS binds more tightly to Zn2+ than do C159A, C176A or C179A
additional information
in silico models of the wild-type and mutated LeuRS CP1 editing domain bound to the analogues with an ester linkage between the amino acid and adenosine as in real substrates [2'-L-leucyladenosine (Leu2A) and 2?-L-norvalyladenosine (Nva2A)] are constructed based on the structure of T252A LeuRS in a complex with tRNALeu and leucyl-adenylate sulphamoyl analogue (Leu-AMS), both positioned in the synthetic active site, and Leu2AA located in the editing domain. The tRNA body dominates the binding energetics of aa-tRNA:LeuRS complex formation
additional information
-
in silico models of the wild-type and mutated LeuRS CP1 editing domain bound to the analogues with an ester linkage between the amino acid and adenosine as in real substrates [2'-L-leucyladenosine (Leu2A) and 2?-L-norvalyladenosine (Nva2A)] are constructed based on the structure of T252A LeuRS in a complex with tRNALeu and leucyl-adenylate sulphamoyl analogue (Leu-AMS), both positioned in the synthetic active site, and Leu2AA located in the editing domain. The tRNA body dominates the binding energetics of aa-tRNA:LeuRS complex formation
additional information
-
mutation of residue T252 leads to incorporation of 2-aminocaprylic acid and of cysteine modified with linear alkyl halides and linear hydrophobic noncanonical amino acids containing functional groups, such as alkyne, azide, ketone, alkene, halogen
additional information
-
construction of deletion mutant LeuRS-A lacking residues Q281 to D294, and of deletion mutant LeuRS-B, lacking residues S295 to L304. The Km values of the two mutants for leucine and ATP decrease slightly and for tRNA increase slightly. The kcat values for the three substrates decrease
additional information
-
replacement of Giardia lamblia eukarya-specific insertion 1, GlESI, by human eukarya-specific insertion 1, HsESI, results in mutant DELTAESI/DELTAHsESI. The mutation impairs leucine activation, aminoacylation and post-transfer editing functions without changing the editing specificity
additional information
-
deletion of the entire LSD1 abolishes synthetic activity of LeuRS
additional information
-
to explore the oncogenic potential of LARS1 over-expression in lung cancer, LARS1 is knocked-down using siRNA. LARS1 knock-down cells show reduced ability to migrate through transwell membrane and to form colonies in both soft agar and culture plate
additional information
the CP1 hairpin of Homo sapiens cytoplasmic LeuRS (hcLeuRS) is deleted or substituted by those from other representative species. Lack of a CP1 hairpin leads to complete loss of aminoacylation, amino acid activation, and tRNA binding, butthe mutants retain post-transfer editing activity. Only the CP1 hairpin from Saccharomyces cerevisiae LeuRS (ScLeuRS) can partly rescue the hcLeuRS functions. Construction of chimeric mutants with the CP1 hairpin of hcLeuRS substituted for that of hcIleRS or hcValRS. The deacylating activity toward mischarged tRNALeu of hcLeuRS-ScCH1 and -ScCH2 decreases by 15% compared to that of hcLeuRS, kinetics comparisons, overview. Further site-directed mutagenesis indicates that the flexibility of small residues and the charge of polar residues in the CP1 hairpin are crucial for the function of LeuRS
additional information
-
the CP1 hairpin of Homo sapiens cytoplasmic LeuRS (hcLeuRS) is deleted or substituted by those from other representative species. Lack of a CP1 hairpin leads to complete loss of aminoacylation, amino acid activation, and tRNA binding, butthe mutants retain post-transfer editing activity. Only the CP1 hairpin from Saccharomyces cerevisiae LeuRS (ScLeuRS) can partly rescue the hcLeuRS functions. Construction of chimeric mutants with the CP1 hairpin of hcLeuRS substituted for that of hcIleRS or hcValRS. The deacylating activity toward mischarged tRNALeu of hcLeuRS-ScCH1 and -ScCH2 decreases by 15% compared to that of hcLeuRS, kinetics comparisons, overview. Further site-directed mutagenesis indicates that the flexibility of small residues and the charge of polar residues in the CP1 hairpin are crucial for the function of LeuRS
additional information
generation of the isolated C-terminal domain of human mt leucyl-tRNA synthetase, and of DELTACterm mutant
additional information
-
generation of the isolated C-terminal domain of human mt leucyl-tRNA synthetase, and of DELTACterm mutant
additional information
siRNA-mediated knockdown of Lars decreases phosphorylated p70 S6 kinase and inhibits the differentiation of C2C12 mouse myoblasts into myotubes, as evidenced by a decreased fusion index and decreased mRNA and protein expression levels of myogenic markers. si-Lars decreases the level of insulin-like growth factor 2 (Igf2) mRNA expression from the early stages of differentiation, indicating the possibility of an association between the mTORIGF2 axis and Lars. But Lars knockdown does not decrease phosphorylated mTOR in differentiated myotubes, nor does it affect the hypertrophy of myotubes as evidenced by measuring their diameters and detecting the mRNA and protein expression of hypertrophy markers
additional information
-
siRNA-mediated knockdown of Lars decreases phosphorylated p70 S6 kinase and inhibits the differentiation of C2C12 mouse myoblasts into myotubes, as evidenced by a decreased fusion index and decreased mRNA and protein expression levels of myogenic markers. si-Lars decreases the level of insulin-like growth factor 2 (Igf2) mRNA expression from the early stages of differentiation, indicating the possibility of an association between the mTORIGF2 axis and Lars. But Lars knockdown does not decrease phosphorylated mTOR in differentiated myotubes, nor does it affect the hypertrophy of myotubes as evidenced by measuring their diameters and detecting the mRNA and protein expression of hypertrophy markers
additional information
-
temperature-sensitive and leucine-auxotroph mutant leu-5
additional information
-
temperature-sensitive and leucine-auxotroph mutant leu-5
additional information
-
the deletion mutant lacking the C-terminal domain, LeuRSDELTA811-967, retains normal editing activity, but has severely reduced aminoacylation activity, deletion of amino acid residues 911-913 of LeuRS enhances the Ile-tRNAIle deacylation activity, without affecting the Ile-tRNALeu deacylation activity, a C-terminally truncated LeuRS can catalyze the first step of the aminoacylation reaction, Leu-AMP formation, but cannot catalyze the second step, transfer of Leu from Leu-AMP to tRNALeu, overview
additional information
-
deletion of the entire LSD1 abolishes synthetic activity of LeuRS
additional information
-
respiratory deficient mutants. The phenotype is a consequence of a mutation in a nuclear gene coding for mitochondrial leucyl-tRNA synthetase
additional information
-
deletions of the C terminus differentially impact the two functions of the enzyme in splicing and aminoacylation in vivo, overview, a five-amino acid C-terminal deletion of LeuRS, which does not complement a null strain, can form a ternary complex with the bI4 intron and its maturase splicing partner, however, the complex fails to stimulate splicing activity, deletion of the entire yeast mitochondrial LeuRS C-terminal domain enhances its aminoacylation and amino acid editing activities
additional information
-
a series of deletions and chimeric variations in the peptide linker of the yeast mitochondrial LeuRS chimeric mutant that is fused to the Escherichia coli LeuRS C-terminal domain extension are created: a four residue deletion mutant of the yeast mitochondrial LeuRS chimera (Ym EcCTD Delta4) stimulates aminoacylation activity significantly compared to that of the chimera enzyme with no deletion within the linker peptide
additional information
-
an eight residue peptide linker deletion mutant that contains three (Ym EcCTD DELTA8/+3), six (Ym EcCTD DELTA8/+6), or nine (Ym EcCTD DELTA8/+9) residues from the Escherichia coli LeuRS linker peptide restors protein stability and activity. Within these three chimeric peptide linker swaps, successive increases in the length of the Escherichia coli chimeric peptide linker decreases aminoacylation activity progressively
additional information
deletion of the leuS gene is lethal. Human cytoplasmic LeuRS can rescue the knock-out strain but not Escherichia coli LeuRS. LeuRS mutant strains T319, D419A, K404Y, S416D, D418R, T347A or T410A are also able to rescue the null mutant
additional information
-
deletion of the leuS gene is lethal. Human cytoplasmic LeuRS can rescue the knock-out strain but not Escherichia coli LeuRS. LeuRS mutant strains T319, D419A, K404Y, S416D, D418R, T347A or T410A are also able to rescue the null mutant
additional information
growth rate of wild-type strain in media containing a large excess of noncognate amino acid norvaline and reduced leucine is reduced to 35%
additional information
-
growth rate of wild-type strain in media containing a large excess of noncognate amino acid norvaline and reduced leucine is reduced to 35%
additional information
-
deletion of the C-terminal domain lowering the kcat by 152fold
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
40
-
2.5 min, 90% loss of activity of mitochondrial enzyme, 5-10 min, 90% loss of cytoplasmic enzyme
49.5
-
50% inactivation, heating of 0.5°C per minute starting at 30°C, mutant A293D
54
-
50% inactivation, heating of 0.5°C per minute starting at 30°C, wild-type enzyme and mutants A293F, A293G, A293R
55
-
50% inactivation, heating of 0.5°C per minute starting at 30°C, mutants A293I and A293Y
additional information
-
the mixed enzyme mutants are not thermostable in contrary to the wild-type enzyme
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
DTT stabilizes
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 10 mg/ml of enzyme, 1 month, partial cleavage of the enzyme into peptides of 63 and 34 kDA occurs, loss of 30% aminoacylation activity
-
4°C, 50 mM potassium phosphate buffer, pH 7.0, 1 mM MgCl2, 0.002 mM L-leucine, 100 mM NaCl, 15% v/v 1,2-propanediol, stable for several weeks
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni-NTA column chromatography
purified by affinity chromatography using His-select resin
recombinant enzyme
recombinant enzyme and beta-subunit from Escherichia coli, to near homogeneity
-
recombinant enzymes from Escherichia coli, leuS' gene product to homogeneity
-
recombinant His-tagged alpha- and beta-subunits from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
recombinant His-tagged enzyme from Escherichia coli strain Rosetta (DE3) by nickel affinity chromatography and dialysis, to homogeneity
recombinant His-tagged enzyme from strain JM109(DE3), 4.6fold to homogeneity
-
recombinant His-tagged GlLeuRS from Escherichia coli strain BL21-Codon Plus(DE3)-RIL by nickel affinity chromatography
-
recombinant His-tagged LeuRS from Escherichia coli strain RosettaTM 2 (DE3) by nickel affinity and anion exchange chromatography, and ethanol precipitation, to 90% purity
-
recombinant His-tagged mutant and His-tagged CP1 domain expressed in Escherichia coli strain Jm109(DE3), to electrophoretic homogeneity
-
recombinant His-tagged PhLeuRS from Escherichia coli strain BL21-Codon Plus(DE3)-RIL by nickel affinity chromatography
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21 by nickel affinity chromatography
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography to homogeneity
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, co-purifying Leu-AMP is removed
recombinant His-tagged wild-type and mutant enzymes from strain BL21(DE3) by nickel affiniry chromatography
-
recombinant His-tagged wild-type and mutant enzymes from strain BL21(DE3) by nickel affinity chromatography
-
recombinant His-tagged wild-type and mutant enzymes from strain BL21(DE3) by nickel affinity chromatography to homogeneity
-
recombinant His6-tagged LeuRS from Escherichia coli strain BL21(DE3) by anion exchange chromatography, gel filtration, and ultrafiltration, co-purification of prolyl-tRNA synthetase, ProRS, and LeuRS, overview
-
recombinant wild-type and mutant enzymes
recombinant wild-type enzyme from overexpression in Escherichia coli, purification of the proteolytically derived fragments from wild-type enzyme preparation
-
using Ni-NTA chromatography
recombinant His-tagged enzyme from Escherichia coli strain Rosetta (DE3) by nickel affinity chromatography and dialysis, to homogeneity
recombinant His-tagged enzyme from Escherichia coli strain Rosetta (DE3) by nickel affinity chromatography and dialysis, to homogeneity
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
2 genes leuS and leuS', overexpression in Escherichia coli BL21(DE3)
-
DNA fragment encoding the fusion protein of Escherichia coli CP1 domain with Aquifex aeolicus beta-subunit and CP1 Escherichia coli beta-like polypeptide are inserted into pET30a by a two step procedure
-
Escherichia coli BL21-Codon Plus (DE3) cells are co-transformed with plasmid pSBETH6-lrsa and pET-15b-lrsb to produce alphabeta-LeuRS with an N-terminal His6 tag
-
expressed in Escherichia coli as a His-tagged fusion protein
expressed in Escherichia coli BL21(DE3) cells
expression and assembly of the 63 and 34 kDa peptides in Escherichia coli strain KL231 cannot complement the deficient temperature-sensitive strain, while expression of peptide fragments derived by cleavage of other peptide bonds leads to assembly of a functional enzyme
-
expression in Escherichia coli
expression of hcLeuRS and DELTAChcLeuRS (a C-terminal 89-amino acid truncated enzyme form) in a baculovirus system
-
expression of His-tagged cytoplasmic LeuRS in Escherichia coli strain RosettaTM 2 (DE3), expression in Spodotera frugiperda cells via baculovirus transfection system
-
expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3), complementation abilities of wild-type and mutant enzymes of yeast null strain HM402 and Escherichia coli strain KL321, overview
-
expression of His-tagged wild-type and mutant enzymes in strain BL21(DE3), subcloning in strain DH5alpha
-
expression of His-tagged wild-type and mutants in Escherichia coli strain SG13009
-
expression of prolyl-tRNA synthetase, ProRS, and LeuRS in a Saccharomyces cerevisiae two-hybrid system, expression of His6-tagged LeuRS in Escherichia coli strain BL21(DE3)
-
expression of the enzyme and the beta-subunit alone in Escherichia coli, the alpha-subunit cannot be expressed stably
-
expression of the His-tagged CP1 domain mutant and isolated CP1 domain in Escherichia coli strain JM109(DE3)
-
gene CDC60, expression of wild-type and mutants in an Escherichia coli BL21 strain
-
gene LARS, recombinant expression of C-terminally His-tagged enzyme in Escherichia coli strain Rosetta (DE3)
gene LARS2, expression analysis, generation of the isolated C-terminal domain of human mt leucyl-tRNA synthetase
gene leuS, expression of His-tagged wild-type and mutant enzymes in strain BL21(DE3)
-
gene leuS, recombinant expression of His-tagged enzyme in Escherichia coli strain Rosetta (DE3)
gene leuS, recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21 from plasmid pRWecLeuRS
individual expression of His-tagged alpha- and beta-subunits in Escherichia coli strain BL21(DE3)
-
mitochondrial isozyme, DNA sequence determination and analysis, expression of the mature enzyme as His-tagged enzyme in Escherichia coli BL21(DE3)
overexpression of His-tagged GlLeuRS in Escherichia coli strain BL21-Codon Plus(DE3)-RIL. Complementation assay of the thermosensitive Escherichia coli KL231 strain
-
overexpression of His-tagged PhLeuRS in Escherichia coli strain BL21-Codon Plus(DE3)-RIL. Complementation assay of the thermosensitive Escherichia coli KL231 strain
-
overexpression of the alpha and beta subunits and the C- and N-terminal parts of the Escherichia coli enzyme in Escherichia coli as monomeric and dimeric mutants, also mixed between the species
-
overexpression of the N-terminal and the C-terminal parts of the enzyme and of the alpha- and beta-subunits of the Aquifex aeolicus enzyme in an Escherichia coli strain as monomeric and dimeric mutants, also mixed between the species
-
recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
recombinant expression of wild-type and mutant enzymes
subcloning in strain DH5alpha, expression of His-tagged wild-type and mutant enzymes in strain BL21(DE3)
-
the gene fragment encoding the editing domain (residues 228-413) is subcloned into the pET3E-His expression plasmid. The plasmid is transformed into the Escherichia coli BL-21(DE3) strain
the mitochondrial isozyme is cloned and expressed in Escherichia coli with the same N-terminus as that processed in the mitochondria of insect cells as His-tagged protein
-
expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
-
expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
-
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the level of LeuRS expression is significantly higher in lactating mammary gland tissue than in pregnancy mammary gland tissue
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
renaturation and refolding of recombinant leuS gene product expressed in Escherichia coli
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
development of a screening platform using scintillation proximity assay technology
drug development
medicine
synthesis
-
two polyspecific LeuRS mutants can efficiently charge several noncanonical amino acids into proteins expressed in mammalian cells, while discriminating against the 20 canonical amino acids. In combination with an opal-suppressing pyrrolysyl pair, the EcLeuRS variants enable site-specific incorporation of different combinations of two distinct noncanonical amino acids into proteins
drug development
-
LeuRS is a potential target for antiparasitic drug development
drug development
leucyl-tRNA synthetase (LeuRS) is an attractive therapeutic target and a target for development of drugs
drug development
Mycobacterium tuberculosis ATCC 25618 / H37Rv
-
leucyl-tRNA synthetase (LeuRS) is an attractive therapeutic target and a target for development of drugs
-
medicine
-
pretreatment of mice with zinc sulfate solution favors to protection of protein synthesis and acceptor activity of tRNALeu against cadmium-induced inhibition. Under co-exposure of mouse liver to cadmium and zinc, activity of the leucyl-tRNA synthetase is at the level of control. Zinc does not influence TUNEL-positive cell number in cadmium-exposed mouse liver
medicine
-
suppression of a tRNA gene mutation by increasing the steady-state levels of its cognate aminoacyl-tRNA synthetase is a model for potential therapies for human pathogenic tRNA mutations
medicine
-
LARS1 plays roles in migration and growth of lung cancer cells, which suggest its potential implication in lung tumorigenesis
medicine
-
the A3243G mutation of the tRNALeu gene causes mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms and 2% of cases of type 2 diabetes. The alteration of aminoacylation of tRNALeu(UUR) caused by the A3243G mutation leads to mitochondrial translational defects and thereby reduces the aminoacylating efficiencies of tRNALeu(UUR) as well as of tRNAAla and tRNAMet. The transfer of human mitochondrial leucyl-tRNA synthetase into the cybrid cells carrying the A3243G mutation improve the efficiency of aminoacylation and stability of mitochondrial tRNAs and then increase the rates of mitochondrial translation and respiration, consequently correcting the mitochondrial dysfunction
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Release 2026.1 (March 2026)
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