Information on EC 6.3.2.13 - UDP-N-acetylmuramoyl-L-alanyl-D-glutamate-2,6-diaminopimelate ligase

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The expected taxonomic range for this enzyme is: Bacteria

EC NUMBER
COMMENTARY hide
6.3.2.13
-
RECOMMENDED NAME
GeneOntology No.
UDP-N-acetylmuramoyl-L-alanyl-D-glutamate-2,6-diaminopimelate ligase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-D-glutamate + meso-2,6-diaminoheptanedioate = ADP + phosphate + UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-gamma-D-glutamyl-meso-2,6-diaminoheptanedioate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
carboxamide formation
-
-
-
-
carboxylic acid amide formation
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Lysine biosynthesis
-
-
peptidoglycan biosynthesis
-
-
Peptidoglycan biosynthesis
-
-
UDP-N-acetylmuramoyl-pentapeptide biosynthesis I (meso-diaminopimelate containing)
-
-
SYSTEMATIC NAME
IUBMB Comments
UDP-N-acetylmuramoyl-L-alanyl-D-glutamate:(L)-meso-2,6-diaminoheptanedioate gamma-ligase (ADP-forming)
Involved in the synthesis of a cell-wall peptide in bacteria. This enzyme adds diaminopimelate in Gram-negative organisms and in some Gram-positive organisms; in others EC 6.3.2.7 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate---L-lysine ligase) adds lysine instead. It is the amino group of the L-centre of the diaminopimelate that is acylated.
CAS REGISTRY NUMBER
COMMENTARY hide
9075-09-6
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
K12
-
-
Manually annotated by BRENDA team
9602
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + dihydrouridine-5'-diphosphate-MurNAc-L-Ala-D-Glu + meso-2,6-diaminoheptanedioate
ADP + phosphate + dihydrouridine-5'-diphosphate-MurNAc-L-Ala-D-Glu-meso-2,6-diaminoheptanedioate
show the reaction diagram
-
-
-
-
ATP + MurNAc-L-Ala-D-Glu + meso-2,6-diaminoheptanedioate
?
show the reaction diagram
-
relative activity wild-type: 14%
-
-
?
ATP + UDP-MurNAc-L-Ala-D-Glu + D-Ala-D-Ala
?
show the reaction diagram
-
relative activity wild-type: 5%
-
-
?
ATP + UDP-MurNAc-L-Ala-D-Glu + D-allo-cystathionine
ADP + phosphate + UDP-MurNAc-L-Ala-D-Glu-D-allo-cystathionine
show the reaction diagram
-
-
-
-
ATP + UDP-MurNAc-L-Ala-D-Glu + D-Glu
?
show the reaction diagram
-
relative activity wild-type: 13%
-
-
?
ATP + UDP-MurNAc-L-Ala-D-Glu + D-Lys
?
show the reaction diagram
-
relative activity wild-type: 9%
-
-
?
ATP + UDP-MurNAc-L-Ala-D-Glu + D-ornithine
?
show the reaction diagram
-
relative activity wild-type: 8%
-
-
?
ATP + UDP-MurNAc-L-Ala-D-Glu + DL-lanthionine
?
show the reaction diagram
-
relative activity wild-type: 82%
-
-
?
ATP + UDP-MurNAc-L-Ala-D-Glu + L-Ala
?
show the reaction diagram
-
relative activity wild-type: 12%
-
-
?
ATP + UDP-MurNAc-L-Ala-D-Glu + L-allo-cystathionine
ADP + phosphate + UDP-MurNAc-L-Ala-D-Glu-L-allo-cystathionine
show the reaction diagram
-
-
-
-
ATP + UDP-MurNAc-L-Ala-D-Glu + L-cystathionine
?
show the reaction diagram
-
relative activity wild-type: 12%
-
-
?
ATP + UDP-MurNAc-L-Ala-D-Glu + L-Lys
?
show the reaction diagram
-
relative activity wild-type: 7%
-
-
?
ATP + UDP-MurNAc-L-Ala-D-Glu + meso-2,6-diaminoheptanedioate
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-gamma-glutamyl-meso-2,6-diaminoheptanedioate
show the reaction diagram
ATP + UDP-MurNAc-L-Ala-D-Glu + meso-lanthionine
ADP + phosphate + UDP-MurNAc-L-Ala-D-Glu-meso-lanthionine
show the reaction diagram
-
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala-D-Glu + meso-diaminopimelic acid
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-D-Glu-meso-diaminopimelic acid
show the reaction diagram
ATP + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate + D-lysine
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-gamma-glutamyl-D-lysine
show the reaction diagram
-
-
-
-
?
ATP + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate + L-lysine
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-gamma-glutamyl-L-lysine
show the reaction diagram
ATP + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate + L-ornithine
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-gamma-glutamyl-L-ornithine
show the reaction diagram
-
-
-
-
?
ATP + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate + meso-2,6-diaminoheptanedioate
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-gamma-glutamyl-meso-2,6-diamino-heptanedioate
show the reaction diagram
ATP + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate + meso-2,6-diaminoheptanedioate
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-gamma-glutamyl-meso-2,6-diaminoheptanedioate
show the reaction diagram
ATP + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate + meso-diaminopimelic acid
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-gamma-glutamyl-meso-diaminopimelic acid
show the reaction diagram
-
-
-
-
?
ATP + UDP-N-MurNAc-L-Ala-D-Glu + meso-2,6-diaminoheptanedioate
?
show the reaction diagram
GTP + UDP-MurNAc-L-Ala-D-Glu + meso-2,6-diaminoheptanedioate
GDP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-gamma-glutamyl-meso-2,6-diaminoheptanedioate
show the reaction diagram
-
relative activity wild-type: 30%
-
-
?
UDP-N-acetylmuramoyl-L-alanyl-D-glutamate + ATP + meso-diaminopimelic acid
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-gamma-glutamyl-meso-diaminopimelic acid
show the reaction diagram
UTP + UDP-MurNAc-L-Ala-D-Glu + meso-2,6-diaminoheptanedioate
UDP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-gamma-glutamyl-meso-2,6-diaminoheptanedioate
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate + meso-2,6-diaminoheptanedioate
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-gamma-glutamyl-meso-2,6-diamino-heptanedioate
show the reaction diagram
ATP + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate + meso-2,6-diaminoheptanedioate
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-gamma-glutamyl-meso-2,6-diaminoheptanedioate
show the reaction diagram
ATP + UDP-N-MurNAc-L-Ala-D-Glu + meso-2,6-diaminoheptanedioate
?
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cd2+
-
can partially substitute for Mg2+
NH4+
-
K+ or NH4+ required
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-methyl-2-[(4Z)-tetradec-4-en-1-yl]quinolin-4(1H)-one
-
inhibitory to enzyme and growth inhibitor of Mycobacterium tuberculosis and rapid-growing mycobacteria
1-methyl-2-[(5Z)-tetradec-5-en-1-yl]quinolin-4(1H)-one
-
inhibitory to enzyme and growth inhibitor of Mycobacterium tuberculosis and rapid-growing mycobacteria
2-[(1E)-dec-1-en-1-yl]-1-methylquinolin-4(1H)-one
-
inhibitory to enzyme and growth inhibitor of Mycobacterium tuberculosis and rapid-growing mycobacteria
2-[(1E)-dodec-1-en-1-yl]-1-methylquinolin-4(1H)-one
-
inhibitory to enzyme and growth inhibitor of Mycobacterium tuberculosis and rapid-growing mycobacteria
2-[(1E)-tridec-1-en-1-yl]-1-methylquinolin-4(1H)-one
-
inhibitory to enzyme and growth inhibitor of Mycobacterium tuberculosis and rapid-growing mycobacteria
Butylamine
-
500 mM, 88% inhibition
Butyrate
-
500 mM, 44% inhibition
ethylamine
-
500 mM, 73% inhibition
methylamine
-
500 mM, 80% inhibition
MurEP1
-
time-dependent inhibition
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MurNAc(alpha-methyl)-L-Ala-D-Glu
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-
MurNAc(beta-methyl)-L-Ala-D-Glu
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-
N-([(2S)-2-[(2-naphthylsulfonyl)amino]propyl]-sulfonyl)-D-glutamic acid
-
60% residual activity at 1 mM
N-([(2S)-2-[([1,1'-biphenyl]-4-yl-sulfonyl)amino]-propyl]sulfonyl)-D-glutamic acid
-
12% residual activity at 1 mM
N-[((2S)-2-[[(E)-3-(1,3-benzodioxol-5-yl)-2-propenoyl]amino]propyl)sulfonyl]-D-glutamic acid
-
64% residual activity at 1 mM
N-[[(2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]sulfonyl]-D-glutamic acid
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41% residual activity at 1 mM
N-[[(2S)-2-([2-[2-(acetylamino)phenoxy]acetyl]-amino)propyl]sulfonyl]-D-glutamic acid
-
56% residual activity at 1 mM
N-[[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-ethyl]sulfonyl]-D-glutamic acid
-
1 mM
Nalpha-Propionyl-L-Ala-2-amino-6-phosphonohexanoate
-
-
Nalpha-Propionyl-L-Ala-3-phosphonoacetamido-Ala
-
-
Nalpha-Propionyl-L-Ala-buthionine sulfoximine
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-
P1-MurNAc-L-Ala-D-Glu
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-
Propionyl-L-Ala-D-Glu(CH2Cl)-OH
-
-
Propionyl-L-Ala-xi-2-amino-4-phosphonobutanoate
-
-
Propylamine
-
500 mM, 87% inhibition
UDP-MurNAc-L-Ala-D-Glu
-
above 0.4 mM
additional information
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-
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.008 - 3.6
ATP
10
D-allo-cystathionine
-
-
1.7
D-Lysine
-
at 68C
0.097
dihydrouridine-5'-diphosphate-MurNAc-L-Ala-D-Glu
-
-
3.9
L-allo-cystathionine
-
-
2.8
L-lysine
-
at 68C
27
L-ornithine
-
at 68C
0.012 - 0.473
meso-2,6-diaminoheptanedioate
0.069 - 4.8
meso-diaminopimelic acid
1.5
meso-lanthionine
-
-
0.005 - 0.148
UDP-MurNAc-L-Ala-D-Glu
0.04
UDP-N-acetylmuramoyl-L-Ala-D-Glu
pH 7.4, 37C
0.03 - 0.45
UDP-N-acetylmuramoyl-L-alanyl-D-glutamate
0.035 - 0.32
UDP-N-MurNAc-L-Ala-D-Glu
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.05 - 1.3
ATP
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.052 - 0.159
1-methyl-2-[(4Z)-tetradec-4-en-1-yl]quinolin-4(1H)-one
0.036 - 0.095
1-methyl-2-[(5Z)-tetradec-5-en-1-yl]quinolin-4(1H)-one
0.07 - 0.207
2-[(1E)-dec-1-en-1-yl]-1-methylquinolin-4(1H)-one
0.072 - 0.187
2-[(1E)-dodec-1-en-1-yl]-1-methylquinolin-4(1H)-one
0.052 - 0.14
2-[(1E)-tridec-1-en-1-yl]-1-methylquinolin-4(1H)-one
0.5 - 0.8
MurEP1
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00259
-
-
0.0047
-
K224A mutant
0.0393
-
-
0.078
-
K224A mutant, in the presence of 500 mM propionate
0.625
recombinant His-tagged MurE
1.24
-
recombinant wild-type MurE
3.31
-
recombinant MurE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8.3 - 9
-
-
8.5 - 9.2
-
vegetative cells
8.8 - 9.9
-
endospores
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.2 - 9.5
-
about 40% of maximal activity at pH 7.2 and 9.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
the enzyme has 25% of its maximum activity at 37C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Escherichia coli (strain K12)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
55000
-
SDS-PAGE
56000
-
SDS-PAGE
62000
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
-
1 * 56000, SDS-PAGE
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystals of native and selenomethionine MurE are grown in the presence of UDP-N-acetylmuramoyl-L-alanyl-D-glutamate, 0.002 ml of protein solution containing 10 mg/ml enzyme, 20 mM HEPES, pH 7.5 200 mM NaCl, 5 mM dithiothreitol and 1 mM UDP-N-acetylmuramoyl-L-alanyl-D-glutamate, are equilibrated together with 0.002 ml reservoir buffer consisting of 100 mM HEPES, pH 7.5, 13% polyethylene glycol monomethyl ether 5000, 500 mM LiCl, 10% isopropanol and 5 mM dithiothreitol, against 1 ml reservoir buffer, crystals diffract to 2.0 A
modeling of the threedimensional structure using comparative modeling methods based on the X-ray crystal structure of MurE from Escherichia coli. The 3D-structure was docked with its substrates meso-diaminopimelic acid and UDP-N-acetylmuramoyl-glycyl-D-glutamate and its product UDP-N-acetyl muramoyl-glycyl-D-Glu-meso-diaminopimelate and also with ATP. The carboxylic acid group of UDP-N-acetylmuramoyl-glycyl-D-glutamate is positioned in proximity to gamma-phosphate of the ATP to facilitate the formation of acylphosphate intermediate. The orientation of an amino group of diaminopimelate facilitates the nucleophilic attack to form the product
computational docking of inhibitors to crystal strucuture. Uracil recognition site is a probable binding site for quinolone inhibitors
-
to 3.0 A resolution in the presence of the substrate UDP-MurNAc-L-Ala-D-Glu. Protein consists of 3 domains consisting of residues 25-139,140-378 and 379-535, respectively. The UAG ligand binds to both domains 1 and 2 with the UDP portion binding to domain 1 and the peptide to domain 2. The substrate molecule UAG is bound between domains 1 and 2
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
10 - 40
purified recombinant His-tagged enzyme, stable up to
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-18C, retains more than 80% of the activity after 3 months
-
-20C, complete loss of activity after 2 d
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Ni2+-nitrilotriacetate-agarose chromatography
-
recombinant His-tagged MurE, Ni2+-nitrilotriacetate agarose
recombinant MurE
-
recombinant MurE, Talon resin
-
using Ni-NTA chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expresision of His-tagged MurE in Escherichia coli
-
expressed in Escherichia coli as a His-tagged fusion protein
-
expressed in Escherichia coli strains BL21(DE3)/pLysS and DH5alpha
-
expression in Escherichia coli
expression of His-tagged MurE and selenomethionine-MurE in Escherichia coli
gene murE or Rv2158c, located in the division/cell wall (dcw) cluster,, identification of a promoter driving the co-transcription of mur synthetases along with key cell division genes such as ftsQ and ftsW, recombinant expression of His6-tagged enzyme in Escherichia coli BL21(DE3)/pLysS and Pseudomonas putida KT2442, subcloning in Escherichia coli strain DH5alpha.. Coexpression of genes murC/D/E/F/nat and genes pknA, pknB, murI, dapF, ddlA, namH, Rv2160c, ftsW, ftsQ, ftsZ, sepF, wag31 in Mycobacterium smegmatis
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D392A
-
kcat lower than wild-type, Km (meso-2,6-diaminoheptanedioate) and Km (ATP) higher than wild-type, Km (UDP-MurNAc-L-Ala-D-Glu) lower than wild-type, mutant shows hydrolysis of ATP uncoupled from catalysis. The ATP hydrolysis rate is enhanced by at least partial occupation of the uridine nucleotide dipeptide binding site, mutant shows very high activity with all the amino acids, uridine sugar precursors and nucleotides tested compared to wild type and moreover, reaching up to 100%
DELTA1-24
-
N-terminal deletion mutant, kcat comparable to wild-type, Km values comparable to wild-type, mutant shows similar results to the wild-type with all the nucleotides, UDP-MurNAc peptides and amino acids
E220A
-
kcat lower than wild-type, Km (ATP) and Km (UDP-MurNAc-L-Ala-D-Glu), Km (meso-2,6-diaminoheptanedioate) lower than wild-type, mutant shows hydrolysis of ATP uncoupled from catalysis. The ATP hydrolysis rate is enhanced by atleast partial occupation of the uridine nucleotide dipeptide binding site, mutant shows very high activity with all the amino acids, uridine sugar precursors and nucleotides tested compared to wild type and moreover, reaching up to 100%
K157A
-
kcat lower than wild-type, Km (meso-2,6-diaminoheptanedioate), Km (UDP-MurNAc-L-Ala-D-Glu) and Km (ATP) lower than wild-type, mutant shows hydrolysis of ATP uncoupled from catalysis. The ATP hydrolysis rate is enhanced by at least partial occupation of the uridine nucleotide dipeptide binding site, mutant shows very high activity with all the amino acids, uridine sugar precursors and nucleotides tested compared to wild type and moreover, reaching up to 100%
N449D
-
kcat lower than wild-type, Km (ATP) and Km (meso-2,6-diaminoheptanedioate) higher than wild-type, Km (UDP-MurNAc-L-Ala-D-Glu) lower than wild-type, mutant shows similar results to the wild-type with all the nucleotides, UDP-MurNAc peptides and amino acids, except D-Lys, which shows a slightly higher activity for mutant N449D
R451A
-
kcat lower than wild-type, Km (ATP) comparable to wild-type, Km (meso-2,6-diaminoheptanedioate) higher than wild-type, Km (UDP-MurNAc-L-Ala-D-Glu) lower than wild-type, significant activity in the presence of L-Lys, D-Lys, DL-ornithine and D-Glu for mutant R451A with similar activities as wild type for all the nucleotides and UDP-MurNAc peptides tested
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