Information on EC 6.3.2.9 - UDP-N-acetylmuramoyl-L-alanine-D-glutamate ligase

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The expected taxonomic range for this enzyme is: Bacteria

EC NUMBER
COMMENTARY
6.3.2.9
-
RECOMMENDED NAME
GeneOntology No.
UDP-N-acetylmuramoyl-L-alanine-D-glutamate ligase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ATP + UDP-N-acetylmuramoyl-L-alanine + D-glutamate = ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate
show the reaction diagram
-
-
-
-
ATP + UDP-N-acetylmuramoyl-L-alanine + D-glutamate = ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate
show the reaction diagram
a tetrahedral transition state follows the acyl phosphate in the reaction pathway
-
ATP + UDP-N-acetylmuramoyl-L-alanine + D-glutamate = ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate
show the reaction diagram
the catalytic mechanism involves a tetrahedral intermediate
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
carboxamide formation
-
-
-
-
carboxylic acid amide formation
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
D-Glutamine and D-glutamate metabolism
-
Metabolic pathways
-
Peptidoglycan biosynthesis
-
UDP-N-acetylmuramoyl-pentapeptide biosynthesis I (meso-DAP-containing)
-
UDP-N-acetylmuramoyl-pentapeptide biosynthesis II (lysine-containing)
-
SYSTEMATIC NAME
IUBMB Comments
UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase (ADP-forming)
Involved with EC 6.3.2.4 (D-alanine---D-alanine ligase), EC 6.3.2.7 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate---L-lysine ligase) or EC 6.3.2.13 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate---2,6-diaminopimelate ligase), EC 6.3.2.8 (UDP-N-acetylmuramate---L-alanine ligase) and EC 6.3.2.10 (UDP-N-acetylmuramoyl-tripeptide---D-alanyl-D-alanine ligase) in the synthesis of a cell-wall peptide (click here for diagram).
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
D-Glutamate-adding enzyme
-
-
-
-
D-glutamic acid adding enzyme
-
-
-
-
D-Glutamic acid-adding enzyme
-
-
-
-
MurD cell wall enzyme
-
-
MurD ligase
-
-
Synthetase, uridine diphospho-N-acetylmuramoylalanyl-D-glutamate
-
-
-
-
UDP-Mur-Nac-L-Ala:L-Glu ligase
-
-
-
-
UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase
-
-
-
-
UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase
-
-
UDP-N-acetylmuramoyl-L-alanine:D-glutamateligase
-
-
UDP-N-acetylmuramoyl-L-alanyl-D-glutamate synthetase
-
-
-
-
UDPMurNAc-L-alanine:D-glutamate ligase (ADP-forming)
-
-
-
-
Uridine diphosphate N-acetylmuramoyl-L-alanine:D-glutamate ligase
-
-
-
-
Uridine diphospho-N-acetylmuramoylalanyl-D-glutamate synthetase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9023-59-0
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
Bacillus subtilis 168
168
-
-
Manually annotated by BRENDA team
JM83(pMLD58)
-
-
Manually annotated by BRENDA team
JM83(pMLD58), overproducing strain
-
-
Manually annotated by BRENDA team
K12 Km83, an overproducing strain that harbours recombinant plasmids bearing the murD gene under the control of the lac Pg promoter, JM83(pDML13) and JM83(pMLD50)
-
-
Manually annotated by BRENDA team
strain DH5alpha
-
-
Manually annotated by BRENDA team
strain JM83(pMLD58)
-
-
Manually annotated by BRENDA team
strain JM83(pMLD58)
UniProt
Manually annotated by BRENDA team
Escherichia coli DH5alpha
strain DH5alpha
-
-
Manually annotated by BRENDA team
Escherichia coli JM83(pMLD58)
JM83(pMLD58)
-
-
Manually annotated by BRENDA team
Escherichia coli JM83(pMLD58)
strain JM83(pMLD58)
-
-
Manually annotated by BRENDA team
Escherichia coli JM83(pMLD58)
strain JM83(pMLD58)
UniProt
Manually annotated by BRENDA team
Escherichia coli K12
K12
-
-
Manually annotated by BRENDA team
Lysinibacillus sphaericus 9602
9602
-
-
Manually annotated by BRENDA team
strain H37Ra, gene m-murD or Rv2155c
-
-
Manually annotated by BRENDA team
clinical isolates of strain R27
Uniprot
Manually annotated by BRENDA team
temperature-sensitive mutants with defective cell wall biosynthesis, TOF-95, TOF-9, TOF-123, TOF-1
-
-
Manually annotated by BRENDA team
Staphylococcus pyogenes
strain MB4439
-
-
Manually annotated by BRENDA team
Staphylococcus pyogenes MB4439
strain MB4439
-
-
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + 1-phospho-N-acetylmuramoyl-L-Ala + Glu
ADP + phosphate + 1-phospho-N-acetylmuramoyl-L-Ala-D-Glu
show the reaction diagram
Escherichia coli, Escherichia coli K12
-
-
-
-
-
ATP + dihydrouridine 5'-diphosphate-N-acetylmuramoyl-L-Ala + Glu
ADP + phosphate + dihydrouridine 5'-diphosphate-N-acetylmuramoyl-L-Ala-D-Glu
show the reaction diagram
Escherichia coli, Escherichia coli K12
-
-
-
-
-
ATP + UDP-N-acetylmuramate-L-alanine
adenosine 5'-tetraphosphate
show the reaction diagram
Escherichia coli, Escherichia coli JM83(pAM1005), Escherichia coli JM83(pMLD58)
-
-
-
?
ATP + UDP-N-acetylmuramate-L-alanine + D-glutamate
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate
show the reaction diagram
-
-
-
-
?
ATP + UDP-N-acetylmuramate-L-alanine + D-glutamate
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate
show the reaction diagram
Escherichia coli, Escherichia coli DH5alpha
-
-
-
r
ATP + UDP-N-acetylmuramoyl-L-Ala + (+/-)trans-1-amino-3-carboxy-cyclohexanecarboxylic acid
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-(+/-)trans-1-amino-3-carboxy-cyclohexanecarboxylic acid
show the reaction diagram
-
-
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + (+/-)trans-1-amino-3-carboxy-cyclopentanecarboxylic acid
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-(+/-)trans-1-amino-3-carboxy-cyclopentanecarboxylic acid
show the reaction diagram
-
-
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + alpha-methyl-DL-Glu
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-alpha-methyl-DL-Glu
show the reaction diagram
-
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + D-erythro-3-methylglutamic acid
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-D-erythro-3-methylglutamic acid
show the reaction diagram
-
-
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + D-erythro-4-methylglutamic acid
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-D-erythro-4-methylglutamic acid
show the reaction diagram
-
-
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + D-Glu
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-D-Glu
show the reaction diagram
-
-
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + D-Glu
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-D-Glu
show the reaction diagram
-
-
-
-
?
ATP + UDP-N-acetylmuramoyl-L-Ala + DL-homocysteic acid
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-DL-homocysteic acid
show the reaction diagram
-
-
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + Glu
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-D-Glu
show the reaction diagram
-
-
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + Glu
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-D-Glu
show the reaction diagram
-
-
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + Glu
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-D-Glu
show the reaction diagram
-
-
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + Glu
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-D-Glu
show the reaction diagram
P14900
-
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + Glu
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-D-Glu
show the reaction diagram
-
-
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + Glu
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-D-Glu
show the reaction diagram
-
-
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + Glu
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-D-Glu
show the reaction diagram
-
r, DL -glutamine
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + Glu
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-D-Glu
show the reaction diagram
-
highly stereospecific for D-Glu
-
-
?
ATP + UDP-N-acetylmuramoyl-L-Ala + Glu
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-D-Glu
show the reaction diagram
Bacillus subtilis 168
-
-
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + Glu
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-D-Glu
show the reaction diagram
Staphylococcus aureus Copenhagen
-
-
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + Glu
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-D-Glu
show the reaction diagram
Escherichia coli K12
-
-
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + Glu
?
show the reaction diagram
-
key role in peptidoglycan biosynthesis
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + Glu
?
show the reaction diagram
P14900
key role in peptidoglycan biosynthesis
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + Glu
?
show the reaction diagram
-
activity is not in excess in the cell under normal growth conditions, but its amount is adjusted to the requirements of peptidoglycan synthesis
-
-
-
ATP + UDP-N-acetylmuramyl-L-alanine + D-glutamate
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate
show the reaction diagram
-
-
-
-
?
ATP + UDP-N-acetylmuramyl-L-alanine + D-glutamate
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate
show the reaction diagram
-
-
-
-
?
ATP + UDP-N-acetylmuramyl-L-alanine + D-glutamate
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate
show the reaction diagram
-
MurD is essential for cytoplasmic bacterial cell wall biosynthesis
-
-
?
ATP + UDP-N-acetylmuramyl-L-alanine + D-glutamate
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate
show the reaction diagram
-
the ligase MurD is involved in the process of peptidoglycan biosynthesis by catalyzing the addition of D-glutamate to the nucleotide precursor UDP-N-acetylmuramoyl-L-alanine
-
-
?
additional information
?
-
-
structure-function analysis by hybrid quantum mechanical/molecular mechanical replica path method, three possible reaction pathways via tetrahedral intermediate, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + UDP-N-acetylmuramoyl-L-Ala + Glu
?
show the reaction diagram
-
key role in peptidoglycan biosynthesis
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + Glu
?
show the reaction diagram
P14900
key role in peptidoglycan biosynthesis
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + Glu
?
show the reaction diagram
-
activity is not in excess in the cell under normal growth conditions, but its amount is adjusted to the requirements of peptidoglycan synthesis
-
-
-
ATP + UDP-N-acetylmuramyl-L-alanine + D-glutamate
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate
show the reaction diagram
-
-
-
-
?
ATP + UDP-N-acetylmuramyl-L-alanine + D-glutamate
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate
show the reaction diagram
-
MurD is essential for cytoplasmic bacterial cell wall biosynthesis
-
-
?
ATP + UDP-N-acetylmuramyl-L-alanine + D-glutamate
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate
show the reaction diagram
-
the ligase MurD is involved in the process of peptidoglycan biosynthesis by catalyzing the addition of D-glutamate to the nucleotide precursor UDP-N-acetylmuramoyl-L-alanine
-
-
?
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
arsenate
-
increases storage stability
Ca2+
-
increases storage stability
Cd2+
-
abolishes the enzyme activity at 5mM
Mg2+
-
optimal concentration: 10 mM
Mg2+
-
optimal concentration: 5-25 mM for the spore enzyme, 6-28 mM for the enzyme from vegetative cells
Mg2+
-
optimal concentration: 10 mM, independent of ATP concentration
Mg2+
-
highly dependent on, optimal concentration: 5 mM
Mg2+
-
increases storage stability
Mg2+
-
required, optimal concentration 15 mM
Mn2+
-
optimal concentration: 1 mM
Mn2+
-
absolute requirement, maximal activity at concentrations of Mn2+ equimolar to ATP
Mn2+
-
increases storage stability
phosphate
-
increases storage stability
potassium phosphate
-
highly dependent on, optimal concentration: 11-16 mM, inhibition above 20 mM
sulfate
-
increases storage stability
vanadate
-
abolishes the enzyme activity at 5mM
Zn2+
-
abolishes the enzyme activity at 5mM
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(2R)-2-[((3-[(Z)-(4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]phenyl)carbonyl)amino]pentanedioic acid
-
-
(2R)-2-[((4-[(Z)-(4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]phenyl)carbonyl)amino]pentanedioic acid
-
-
(2R)-2-[[(7-(2-ethoxy-2-oxoethoxy)naphthalen-2-yl)sulfonyl]amino]pentanedioic acid
-
NMR and molecular dynamics analysis
(2R)-2-[[(7-(3-phenylpropoxy)naphthalen-2-yl)sulfonyl]amino]pentanedioic acid
-
NMR and molecular dynamics analysis
(2R)-2-[[(7-(4-cyanobenzyloxy)naphthalen-2-yl)sulfonyl]amino]pentanedioic acid
-
NMR and molecular dynamics analysis
(2R)-2-[[(7-(4-cyanobenzyloxy)naphthalen-2-yl)sulfonyl]amino]pentanedioic acid
-
calculation of binding free energies. Main driving force for binding are non-polar van der Waals-interactions
(2R)-2-[[(7-benzyloxynaphthalen-2-yl)sulfonyl]amino]pentanedioic acid
-
calculation of binding free energies. Main driving force for binding are non-polar van der Waals-interactions
(2R)-2-[[(7-butoxynaphthalen-2-yl)sulfonyl]amino]pentanedioic acid
-
NMR and molecular dynamics analysis
(2R)-2-[[(7-pentoxynaphthalen-2-yl)sulfonyl]amino]pentanedioic acid
-
calculation of binding free energies. Main driving force for binding are non-polar van der Waals-interactions
(2S)-2-[((4-[(Z)-(4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]phenyl)carbonyl)amino]pentanedioic acid
-
-
(R,Z)-2-(3-((1-carboxy-N-(4-((4-oxo-2-thioxothiazolidin-5-ylidene)-methyl)phenyl)formamido)methyl)benzamido)pentanedioic acid
-
-
(R,Z)-2-(3-((2-carboxy-N-(4-((4-oxo-2-thioxothiazolidin-5-ylidene)-methyl)phenyl)acetamido)methyl)benzamido)pentanedioic acid
-
in addition, weak activity against Gram-positive Staphylococcus aureus and Enterococcus faecalis
(R,Z)-2-(3-((3-carboxy-N-(4-((4-oxo-2-thioxothiazolidin-5-ylidene)-methyl)phenyl)propanamido)methyl)benzamido)pentanedioic acid
-
in addition, weak activity against Gram-positive Staphylococcus aureus and Enterococcus faecalis
(R,Z)-2-(3-((4-((2,4-dioxothiazolidin-5-ylidene)methyl)phenylamino)methyl)benzamido)pentanedioic acid
-
-
(R,Z)-2-(3-((4-((4-oxo-2-thioxothiazolidin-5-ylidene)methyl)phenylamino)methyl)benzamido)pentanedioic acid
-
-
-
1-Phospho-N-acetylmuramoyl-L-Ala-D-Glu
-
-
2,3,4,5-tetrabromo-6-(3,6-dihydroxy-9H-xanthen-9-yl)benzoic acid
-
inhibitor identified by structure-based virtual screening
2,4,6-Trinitrobenzenesulfonic acid
-
-
2-((4-[(2S)-butan-2-ylamino]-6-(ethylamino)-1,3,5-triazin-2-yl)sulfanyl)-N-(2-chlorophenyl)acetamide
-
0.5 mM, 50% inhibition. Inhibitory to both MurC and MurD, ECs 6.3.2.8 and 6.3.2.9, respectively
2-([2-(2-naphthylsulfonyl)hydrazono)methyl]phenyl 2-nitrobenzenesulfonate
-
71% inhibition at 0.05 mM
2-([2-(2-naphthylsulfonyl)hydrazono)methyl]phenyl 3-nitrobenzenesulfonate
-
70% inhibition at 0.05 mM
2-([2-(2-naphthylsulfonyl)hydrazono)methyl]phenyl 4-nitrobenzenesulfonate
-
-
2-([2-(naphthalen-2-ylsulfonyl)hydrazono]methyl)phenyl 2-(benzo[d][1,3]dioxol-5-yl)acetate
-
49% inhibition at 0.10 mM
2-bromo-N-(4-([2-(2-naphthylsulfonyl)hydrazono]methyl)phenyl)benzamide
-
-
2-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]-5-hydroxybenzoic acid
-
-
2-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]benzene-1,4-dicarboxylic acid
-
-
3-([[(5-amino-1,3,4-thiadiazol-2-yl)sulfanyl]acetyl]amino)-4-methylbenzoic acid
-
-
3-bromo-N-(4-([2-(2-naphthylsulfonyl)hydrazono]methyl)phenyl)benzamide
-
-
4-([(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl)-6-(naphthalen-2-ylmethyl)-1,3,5-triazin-2-amine
-
0.5 mM, 33% inhibition. Inhibitory to both MurC and MurD, ECs 6.3.2.8 and 6.3.2.9, respectively
4-cyano-N-(4-([2-(2-naphthylsulfonyl)hydrazono]methyl)phenyl)benzamide
-
78% inhibition at 0.05 mM
4-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]benzene-1,3-dicarboxylic acid
-
-
4-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]cyclohexane-1,3-dicarboxylic acid
-
-
6-([(1,1-dioxidotetrahydrothiophen-3-yl)sulfanyl]methyl)-N-(2-phenylethyl)-1,3,5-triazine-2,4-diamine
-
0.25 mM, 11% inhibition. Inhibitory to both MurC and MurD, ECs 6.3.2.8 and 6.3.2.9, respectively
6-[(1-methyl-1H-imidazol-2-yl)sulfanyl]-N,N'-diphenyl-1,3,5-triazine-2,4-diamine
-
0.5 mM, 30% inhibition. Inhibitory to both MurC and MurD, ECs 6.3.2.8 and 6.3.2.9, respectively
benzylidene rhodanines
-
possess MurC inhibitory activity in the low micromolar range
-
beta,gamma-methyleneadenosine 5'-triphosphate
-
nonhydrolyzable ATP analogue
CPAHWPHPC
-
i.e. peptide MD-C7C_1, inhibits MurD
CSAWSNKFC
-
i.e. peptide MD-C7C_2, inhibits MurD
D-2-Aminoadipic acid
-
-
D-erythro-3-Methylglutamic acid
-
-
D-erythro-4-Methylglutamic acid
-
-
D-Pyroglutamic acid
-
-
dihydrouridine 5'-diphosphate-N-acetylmuramoyl-L-Ala-D-Glu
-
-
DL-2-Amino-4-phosphonobutyric acid
-
-
DL-2-aminopimelic acid
-
-
DL-homocysteic acid
-
-
HSSWYIQHFPPL
-
i.e. peptide MD-12, inhibits MurD
L-Glu
-
50 mM, product inhibition
N'-((2-[(2-nitrobenzyl)oxy]phenyl)methylidene)-2-naphthalenesulfonohydrazide
-
-
N'-((2-[(3-nitrobenzyl)oxy]phenyl)methylidene)-2-naphthalenesulfonohydrazide
-
70% inhibition at 0.05 mM
N'-((2-[(4-cyanobenzyl)oxy]phenyl)methylidene)(2-fluorophenyl)methanesulfonohydrazide
-
39% inhibition at 0.10 mM
N'-((2-[(4-cyanobenzyl)oxy]phenyl)methylidene)(phenyl)methanesulfonohydrazide
-
58% inhibition at 0.10 mM
N'-((2-[(4-cyanobenzyl)oxy]phenyl)methylidene)-2-naphthalenesulfonohydrazide
-
-
N'-((2-[(4-cyanobenzyl)oxy]phenyl)methylidene)-2-nitrobenzenesulfonohydrazide
-
86% inhibition at 0.10 mM
N'-((2-[(4-cyanobenzyl)oxy]phenyl)methylidene)-3-nitrobenzenesulfonohydrazide
-
74% inhibition at 0.10 mM
N'-((2-[(4-cyanobenzyl)oxy]phenyl)methylidene)[4-(trifluoromethyl)phenyl]methanesulfonohydrazide
-
57% inhibition at 0.10 mM
N'-((3-[(3-nitrobenzyl)oxy]phenyl)methylidene)-2-naphthalenesulfonohydrazide
-
61% inhibition at 0.05 mM
N-(2-([2-(2-naphthylsulfonyl)hydrazono]methyl)phenyl)-3,5-dinitrobenzamide
-
-
N-(2-([2-(2-naphthylsulfonyl)hydrazono]methyl)phenyl)-4-nitrobenzamide
-
-
N-(3-[[(carboxyacetyl)[4-[(Z)-(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]phenyl]amino]methyl]benzoyl)-D-glutamic acid
-
-
N-(4-([2-(2-naphthylsulfonyl)hydrazono]methyl)phenyl)-2-naphthamide
-
19% inhibition at 0.01 mM
N-(4-([2-(2-naphthylsulfonyl)hydrazono]methyl)phenyl)-2-nitrobenzamide
-
-
N-(4-([2-(2-naphthylsulfonyl)hydrazono]methyl)phenyl)-3,5-dinitrobenzamide
-
78% inhibition at 0.10 mM
N-(4-([2-(2-naphthylsulfonyl)hydrazono]methyl)phenyl)-4-nitrobenzamide
-
81% inhibition at 0.05 mM
N-(4-([2-(2-naphthylsulfonyl)hydrazono]methyl)phenyl)benzamide
-
56% inhibition at 0.10 mM
N-(6-butoxy-naphthalene-2-sulfonyl)-D-glutamic acid
-
competitive versus D-Glu, non-competitive versus ATP and UDP-N-acetylmuramoyl-L-Ala
N-(6-butoxy-naphthalene-2-sulfonyl)-L-glutamic acid
-
competitive versus D-Glu, non-competitive versus UDP-N-acetylmuramoyl-L-Ala
N-([(2S)-2-[(2-naphthylsulfonyl)amino]propyl]-sulfonyl)-D-glutamic acid
-
1 mM, 75% residual activity
N-([(2S)-2-[([1,1'-biphenyl]-4-yl-sulfonyl)amino]-propyl]sulfonyl)-D-glutamic acid
-
1 mM, 70% residual activity
N-[((2S)-2-[[(E)-3-(1,3-benzodioxol-5-yl)-2-propenoyl]amino]propyl)sulfonyl]-D-glutamic acid
-
1 mM, 80% residual activity
N-[2-fluoro-5-[([4-[(Z)-(4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]phenyl]amino)methyl]benzoyl]-D-glutamic acid
-
-
N-[[(2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]sulfonyl]-D-glutamic acid
-
1 mM, 74% residual activity
N-[[(2S)-2-([2-[2-(acetylamino)phenoxy]acetyl]-amino)propyl]sulfonyl]-D-glutamic acid
-
1 mM, 93% residual activity
N-[[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-ethyl]sulfonyl]-D-glutamic acid
-
1 mM, 77% residual activity
Phosphinate
-
an analogue of UDP-N-acetylmuramoyl-dipeptide, the N-acetylmuramoyl moiety being replaced by a hexanoyl chain and the peptide bond between L-Ala and D-Glu by a tetrahedral phosphinate bond
potassium phosphate
-
highly dependent on, optimal concentration: 11-16 mM, inhibition above 20 mM, phosphate ion is responsible for inhibition
RPTHSPI
-
peptides are synthesized from consensus sequences to evaluate their inhibitory potential against the essential MurD enzyme. The C-7-C mers MurDp1 (RPTHSPI) gives a decrease of MurD ATPase activity with a significant IC50 value of 4 mM. The 12 mers MurDp2 (HLPTSSLFDTTG) inhibits MurD with an IC50 value of 15 mM indicating a weak inhibition. Both peptides show a correlation between an increase in concentration versus an increase in inhibition values
UDP-N-acetylmuramoyl-L-Ala-D-Glu
-
-
[1-[(6-Uridinediphospho)hexanamido]ethyl](2,4-dicarboxybutyl)phosphinate pentasodium salt
-
good inhibitor, closely resembles the tetrahedral intermediate that is presumed to form the ligation reaction
additional information
-
synthesis and evaluation of a series of transition-state analog inhibitors
-
additional information
-
design of peptidomimetic lead compounds with the ultimate objective of small molecule chemotherapeutic development, affinity selection by immobilized MurD with addition of ATP in an attempt to achieve conformationally homogenous population of target enzymes, overview. No inhibition by peptide MD-C7C_3, i.e. CQSSPHMSC
-
additional information
-
design and synthesis of N-benzylidenesulfonohydrazide inhibitors of MurC as antibacterial agents
-
additional information
Q8F7V4
generation of MurD 3D models using crystal structures of PDB entries 1EEH and 2JFF as templates in Modeller9v7 and generation of an in-house library of 1,496 MurD inhibitor analogs. Virtual screening of the best-ranked compounds with pharmacokinetics property prediction has provided 17 MurD inhibitors for developing anti-leptospirosis drug targeting peptidoglycan biosynthesis pathway
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.2
-
1-phospho-N-acetylmuramoyl-L-Ala
-
-
0.03
-
ATP
-
pH 9.4, 37C, E157A mutant protein
0.085
-
ATP
-
pH 9.4, 37C, E157K mutant protein
0.095
-
ATP
-
-
0.106
-
ATP
-
37C
0.114
-
ATP
-
pH 9.4, 37C, D35A mutant protein
0.129
-
ATP
-
pH 9.4, 37C, K198F mutant protein
0.13
-
ATP
-
pH 9.4, 37C, H183A mutant protein
0.135
-
ATP
-
pH 9.4, 37C, K198A mutant protein
0.14
-
ATP
-
pH 9.4, 37C, N268A mutant protein
0.144
-
ATP
-
pH 9.4, 37C, Y194F mutant protein
0.153
-
ATP
-
pH 9.4, 37C, H301A mutant protein
0.183
-
ATP
-
pH 9.4, 37C, R425A mutant protein
0.328
-
ATP
-
pH 9.4, 37C, K115A mutant protein
1.58
-
ATP
-
pH 9.4, 37C, N271A mutant protein
2
-
ATP
-
pH 9.4, 37C, R302A mutant protein
2.18
-
ATP
-
pH 9.4, 37C, D317A mutant protein
5.4
-
ATP
-
pH 8.8, 37C
0.055
-
D-Glu
-
-
0.09
-
D-Glu
-
-
0.13
-
D-Glu
-
-
0.13
-
D-Glu
-
pH 8.8, 37C
0.155
-
D-Glu
-
-
0.28
-
D-Glu
-
-
0.044
-
D-glutamate
-
pH 9.4, 37C, D317A mutant protein
0.053
-
D-glutamate
-
pH 9.4, 37C, N271A mutant protein; pH 9.4, 37C, Y194F mutant protein
0.056
-
D-glutamate
-
pH 9.4, 37C, E157K mutant protein
0.067
-
D-glutamate
-
37C
0.074
-
D-glutamate
-
pH 9.4, 37C, R302A mutant protein
0.095
-
D-glutamate
-
pH 9.4, 37C, D35A mutant protein; pH 9.4, 37C, H301A mutant protein
0.128
-
D-glutamate
-
pH 9.4, 37C, K115A mutant protein
0.185
-
D-glutamate
-
pH 9.4, 37C, K198A mutant protein
0.216
-
D-glutamate
-
pH 9.4, 37C, K198F mutant protein
0.264
-
D-glutamate
-
pH 9.4, 37C, N268A mutant protein
0.806
-
D-glutamate
-
pH 9.4, 37C, H183A mutant protein
5.16
-
D-glutamate
-
pH 9.4, 37C, R425A mutant protein
0.01
-
dihydrouridine 5'-diphosphate-N-acetylmuramoyl-L-Ala
-
-
0.138
-
MgATP2-
-
-
0.0073
-
UDP-N-acetylmuramate-L-alanine
-
37C
0.012
-
UDP-N-acetylmuramoyl L-alanine
-
pH 9.4, 37C, N268A mutant protein
0.016
-
UDP-N-acetylmuramoyl L-alanine
-
pH 9.4, 37C, N271A mutant protein
0.04
-
UDP-N-acetylmuramoyl L-alanine
-
pH 9.4, 37C, H301A mutant protein
0.046
-
UDP-N-acetylmuramoyl L-alanine
-
pH 9.4, 37C, K115A mutant protein
0.053
-
UDP-N-acetylmuramoyl L-alanine
-
pH 9.4, 37C, R425A mutant protein
0.057
-
UDP-N-acetylmuramoyl L-alanine
-
pH 9.4, 37C, D317A mutant protein
0.059
-
UDP-N-acetylmuramoyl L-alanine
-
pH 9.4, 37C, H183A mutant protein
0.065
-
UDP-N-acetylmuramoyl L-alanine
-
pH 9.4, 37C, R302A mutant protein
0.084
-
UDP-N-acetylmuramoyl L-alanine
-
pH 9.4, 37C, D35A mutant protein
0.111
-
UDP-N-acetylmuramoyl L-alanine
-
pH 9.4, 37C, Y194F mutant protein
0.12
-
UDP-N-acetylmuramoyl L-alanine
-
pH 9.4, 37C, K198A mutant protein
0.14
-
UDP-N-acetylmuramoyl L-alanine
-
pH 9.4, 37C, K198F mutant protein
0.218
-
UDP-N-acetylmuramoyl L-alanine
-
pH 9.4, 37C, E157K mutant protein
0.304
-
UDP-N-acetylmuramoyl L-alanine
-
pH 9.4, 37C, E157A mutant protein
0.16
-
UDP-N-acetylmuramoyl-Ala
-
-
0.0055
-
UDP-N-acetylmuramoyl-L-Ala
-
-
0.006
-
UDP-N-acetylmuramoyl-L-Ala
-
-
0.0075
-
UDP-N-acetylmuramoyl-L-Ala
-
-
0.03
-
UDP-N-acetylmuramoyl-L-Ala
-
-
0.041
-
UDP-N-acetylmuramoyl-L-Ala
-
pH 8.8, 37C
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0003
-
D-glutamate
-
pH 9.4, 37C, E157K mutant protein
0.0004
-
D-glutamate
-
pH 9.4, 37C, H183A mutant protein
0.004
-
D-glutamate
-
pH 9.4, 37C, K115A mutant protein
0.012
-
D-glutamate
-
pH 9.4, 37C, K198F mutant protein
0.016
-
D-glutamate
-
pH 9.4, 37C, K198A mutant protein
0.022
-
D-glutamate
-
pH 9.4, 37C, D317A mutant protein
0.093
-
D-glutamate
-
pH 9.4, 37C, Y194F mutant protein
0.3
-
D-glutamate
-
pH 9.4, 37C, N271A mutant protein
0.53
-
D-glutamate
-
pH 9.4, 37C, R425A mutant protein
0.77
-
D-glutamate
-
pH 9.4, 37C, H301A mutant protein
3
6
D-glutamate
-
pH 9.4, 37C, R302A mutant protein
3.13
-
D-glutamate
-
pH 9.4, 37C, D35A mutant protein; pH 9.4, 37C, R302A mutant protein
3.3
-
D-glutamate
-
pH 9.4, 37C, N268A mutant protein
4.27
-
D-glutamate
-
pH 9.4, 37C, D35A mutant protein
5.12
-
D-glutamate
-
pH 9.4, 37C, N268A mutant protein
6.08
-
D-glutamate
-
pH 9.4, 37C, H301A mutant protein; pH 9.4, 37C, R425A mutant protein
additional information
-
additional information
-
-
-
additional information
-
additional information
-
turnover of 6.55 at saturation concentrations of all the substrates: 5 mM ATP, 0.25 mM UDP-N-acetylmuramoyl L-alanine, 0.55 mM D-glutamate
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.032
-
2-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]-5-hydroxybenzoic acid
-
pH 8.6, 37C
0.026
-
2-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]benzene-1,4-dicarboxylic acid
-
pH 8.6, 37C
0.0058
-
4-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]benzene-1,3-dicarboxylic acid
-
pH 8.6, 37C
0.125
-
4-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]cyclohexane-1,3-dicarboxylic acid
-
pH 8.6, 37C
15
-
HLPTSSLFDTTG
-
-
0.24
-
N-(6-butoxy-naphthalene-2-sulfonyl)-D-glutamic acid
-
versus D-Glu
0.71
-
N-(6-butoxy-naphthalene-2-sulfonyl)-D-glutamic acid
-
versus UDP-N-acetylmuramoyl-L-Ala
1.66
-
N-(6-butoxy-naphthalene-2-sulfonyl)-D-glutamic acid
-
versus ATP
0.87
-
N-(6-butoxy-naphthalene-2-sulfonyl)-L-glutamic acid
-
versus D-Glu
2.13
-
N-(6-butoxy-naphthalene-2-sulfonyl)-L-glutamic acid
-
versus UDP-N-acetylmuramoyl-L-Ala
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.089
-
(2R)-2-[((3-[(Z)-(4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]phenyl)carbonyl)amino]pentanedioic acid
-
pH not specified in the publication, temperature not specified in the publication
0.045
-
(2R)-2-[((4-[(Z)-(4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]phenyl)carbonyl)amino]pentanedioic acid
-
pH not specified in the publication, temperature not specified in the publication
0.192
-
(2R)-2-[[(7-(2-ethoxy-2-oxoethoxy)naphthalen-2-yl)sulfonyl]amino]pentanedioic acid
-
-
0.132
-
(2R)-2-[[(7-(3-phenylpropoxy)naphthalen-2-yl)sulfonyl]amino]pentanedioic acid
-
-
0.105
-
(2R)-2-[[(7-(4-cyanobenzyloxy)naphthalen-2-yl)sulfonyl]amino]pentanedioic acid
-
-
0.239
-
(2R)-2-[[(7-benzyloxynaphthalen-2-yl)sulfonyl]amino]pentanedioic acid
-
-
0.18
-
(2R)-2-[[(7-butoxynaphthalen-2-yl)sulfonyl]amino]pentanedioic acid
-
-
0.17
-
(2R)-2-[[(7-pentoxynaphthalen-2-yl)sulfonyl]amino]pentanedioic acid
-
-
0.01
-
(2S)-2-[((4-[(Z)-(4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]phenyl)carbonyl)amino]pentanedioic acid
-
pH not specified in the publication, temperature not specified in the publication
0.005
-
(R,Z)-2-(3-((1-carboxy-N-(4-((4-oxo-2-thioxothiazolidin-5-ylidene)-methyl)phenyl)formamido)methyl)benzamido)pentanedioic acid
-
pH not specified in the publication, temperature not specified in the publication. Malachite green assay in presence of 0.01% Triton X-100
0.003
-
(R,Z)-2-(3-((2-carboxy-N-(4-((4-oxo-2-thioxothiazolidin-5-ylidene)-methyl)phenyl)acetamido)methyl)benzamido)pentanedioic acid
-
pH not specified in the publication, temperature not specified in the publication. Malachite green assay in presence of 0.01% Triton X-100
0.007
-
(R,Z)-2-(3-((3-carboxy-N-(4-((4-oxo-2-thioxothiazolidin-5-ylidene)-methyl)phenyl)propanamido)methyl)benzamido)pentanedioic acid
-
pH not specified in the publication, temperature not specified in the publication. Malachite green assay in presence of 0.01% Triton X-100
0.085
-
(R,Z)-2-(3-((4-((2,4-dioxothiazolidin-5-ylidene)methyl)phenylamino)methyl)benzamido)pentanedioic acid
-
pH 8.0, 37C
0.045
-
(R,Z)-2-(3-((4-((4-oxo-2-thioxothiazolidin-5-ylidene)methyl)phenylamino)methyl)benzamido)pentanedioic acid
-
pH 8.0, 37C
-
0.01
-
2,3,4,5-tetrabromo-6-(3,6-dihydroxy-9H-xanthen-9-yl)benzoic acid
-
pH 8.0, 37C
0.074
-
2-([2-(2-naphthylsulfonyl)hydrazono)methyl]phenyl 4-nitrobenzenesulfonate
-
pH 8.0, 37C
0.055
-
2-bromo-N-(4-([2-(2-naphthylsulfonyl)hydrazono]methyl)phenyl)benzamide
-
pH 8.0, 37C
0.046
-
2-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]-5-hydroxybenzoic acid
-
pH 8.6, 37C
0.038
-
2-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]benzene-1,4-dicarboxylic acid
-
pH 8.6, 37C
0.105
-
3-([[(5-amino-1,3,4-thiadiazol-2-yl)sulfanyl]acetyl]amino)-4-methylbenzoic acid
-
37C
0.03
-
3-bromo-N-(4-([2-(2-naphthylsulfonyl)hydrazono]methyl)phenyl)benzamide
-
pH 8.0, 37C
0.0084
-
4-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]benzene-1,3-dicarboxylic acid
-
pH 8.6, 37C
0.182
-
4-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]cyclohexane-1,3-dicarboxylic acid
-
pH 8.6, 37C
0.177
-
beta,gamma-methyleneadenosine 5'-triphosphate
-
37C
1.5
-
CPAHWPHPC
-
pH 8.0, 37C
0.62
-
CSAWSNKFC
-
pH 8.0, 37C
0.07
-
N'-((2-[(2-nitrobenzyl)oxy]phenyl)methylidene)-2-naphthalenesulfonohydrazide
-
pH 8.0, 37C
0.062
-
N'-((2-[(4-cyanobenzyl)oxy]phenyl)methylidene)-2-naphthalenesulfonohydrazide
-
pH 8.0, 37C
0.015
-
N-(3-[[(carboxyacetyl)[4-[(Z)-(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]phenyl]amino]methyl]benzoyl)-D-glutamic acid
-
pH not specified in the publication, temperature not specified in the publication. Malachite green assay in presence of 0.01% Triton X-100
0.045
-
N-(4-([2-(2-naphthylsulfonyl)hydrazono]methyl)phenyl)-2-nitrobenzamide
-
pH 8.0, 37C
0.28
-
N-(6-butoxy-naphthalene-2-sulfonyl)-D-glutamic acid
-
-
0.71
-
N-(6-butoxy-naphthalene-2-sulfonyl)-L-glutamic acid
-
-
0.252
-
N-[2-fluoro-5-[([4-[(Z)-(4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]phenyl]amino)methyl]benzoyl]-D-glutamic acid
-
pH not specified in the publication, temperature not specified in the publication. Malachite green assay in presence of 0.01% Triton X-100
15
-
RPTHSPI
-
peptides are synthesized from consensus sequences to evaluate their inhibitory potential against the essential MurD enzyme. The C-7-C mers MurDp1 (RPTHSPI) gives a decrease of MurD ATPase activity with a significant IC50 value of 4 mM. The 12 mers MurDp2
0.14
-
HSSWYIQHFPPL
-
pH 8.0, 37C
additional information
-
additional information
-
peptides are synthesized from consensus sequences to evaluate their inhibitory potential against the essential MurD enzyme. The C-7-C mers MurDp1 gives a decrease of MurD ATPase activity with a significant IC50 value of 4 mM. The 12 mers MurDp2 inhibits MurD with an IC50 value of 15 mM
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.261
-
-
Escherichia coli JM83(pDML13)
1.772
-
-
37C
1.92
-
-
Escherichia coli JM83 (pMLD50)
5
-
P0A091
25C
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
8
-
-
assay at
8.9
9.2
-
-
9.4
10.5
-
enzyme from spores
9.5
10.5
-
enzyme from vegetative cells
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
Bacillus subtilis 168
-
-
-
Manually annotated by BRENDA team
-
specific activity decays by 50% after the end of exponential cell division
Manually annotated by BRENDA team
Bacillus subtilis 168
-
-
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Bacillus subtilis 168
-
-
-
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Streptococcus agalactiae serotype V (strain ATCC BAA-611 / 2603 V/R)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
46840
-
-
mass spectrometry
52000
-
-
gel filtration
52000
-
P0A091
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 46983, calculation from nucleotide sequence
?
-
x * 51000, SDS-PAGE
additional information
-
all Mur ligases are topologically similar to each other, extremely flexible, and built of three domains connected by two hinges. Each domain binds one of the three substrates, i.e. ATP, growing nucleotide, or the appropriate amino acid
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phosphoprotein
-
the mycobacterial eukaryotic-type serine/threonine kinase PknA transphosphorylates MurD
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
crystal structure of the complexes: MurD-UDP-N-acetylmurmoly-L-alanine -Mg2+ ADP, MurD-UDP-N-acetylmurmoly-L-alanine-D-glutamate and MurD-UDP-N-acetylmurmoly-L-alanine -Mn2+ ADP
P14900
crystal structure of the enzyme in presence of its substrate UDP-N-acetylmuramoyl-L-Ala, at 1.9 A resolution
-
crystal structure of the open enzyme where the C-terminal domain is rotated away from the N-terminal and central domains; crystal structure of the open enzyme where the C-terminal domain is rotated away from the N-terminal and central domains, complexed with UDP-N-acetylmurmoly-L-alanine
-
hanging-drop vapor diffusion technique
-
in complex with inhibitor 4-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]cyclohexane-1,3-dicarboxylic acid. Only one stereoisomer is seen in the co-crystal structure. The absolute configuration of the crystallised compound is (1R,3R,4S).The carboxyl groups at positions 1 and 3 of the rigid cyclohexyl mimetic of D-glutamic acid occupy exactly the same position as the carboxyl groups of the product UDP-MurNAc-L-Ala-D-Glu. The carboxyl group at position 3 of the cyclohexyl ring of the inhibitor forms a charge-based interaction with N of Lys348, and is additionally hydrogen-bonded with a conserved water molecule, W38, which is further hydrogen-bonded to Ogamma of Thr321 and the carboxyl group of Asp182. The carboxyl group at position 1 of the cyclohexyl ring is held in place by hydrogen bonds with Ogamma of Ser415 and the backbone nitrogen of Phe422. The sulfonic group makes hydrogen bonds with His183 and water molecules W183, W242 and W415
-
moelcular docking of inhibitor 6_3_2-9_4-R16
-
structure of MurD in complex with (R,Z)-2-(3-((4-((2,4-dioxothiazolidin-5-ylidene)methyl)phenylamino)methyl)benzamido)pentanedioic acid
-
vapour-diffusion method and hanging-drop system, high resolution crystal structures of MurD in complexes with two novel inhibitors designed to mimic the transition state of the reaction, N-(6-butoxy-naphthalene-2-sulfonyl)-D-glutamic acid or N-(6-butoxy-naphthalene-2-sulfonyl)-Lglutamic acid
-
generation of MurD 3D models using crystal structures of PDB entries 1EEH and 2JFF as templates in Modeller9v7
Q8F7V4
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, 20 mM potassium phosphate, pH 7.0, 1 mM 2-mercaptoethanol, 0.1 mM MgCl2, several months, no loss of activity at high enzyme concentrations: 1-10 mg/ml
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-20C, 20 mM potassium phosphate, pH 7.0, 1 mM dithiothreitol, 0.1 mM MgCl2, several months, no loss of activity at high enzyme concentrations: 1-10 mg/ml
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8C, 20 mM potassium phosphate, pH 7.0, 1 mM 2-mercaptoethanol, 0.1 mM MgCl2, 1 week, 30% loss of activity
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8C, 20 mM potassium phosphate, pH 7.0, 1 mM 2-mercaptoethanol, 0.1 mM MgCl2, sodium Hepes, 1 week, 35-43% loss of activity
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8C, 20 mM potassium phosphate, pH 7.0, 1 mM dithiothreitol, 0.1 mM MgCl2, 1 week, 30% loss of activity
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8C, 20 mM potassium phosphate, pH 7.0, 1 mM dithiothreitol, 0.1 mM MgCl2, sodium Hepes 1 week, 35-43% loss of activity
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8C, 20 mM potassium phosphate, pH 8.0, 1 mM 2-mercaptoethanol, 0.1 mM MgCl2, sodium Hepes, 1 week, 35-43% loss of activity
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8C, 20 mM potassium phosphate, pH 8.0, 1 mM dithiothreitol, 0.1 mM MgCl2, sodium Hepes 1 week, 35-43% loss of activity
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-18C, 20-30% loss of activity
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Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
method that includes DEAE-Trisacryl M and hydroxyapatite-Ultrogel chromatography. Large-scale purification using 2-mercaptoethanol as a reducing agent, results in 200 mg of purified enzyme from 54 l of culture, adducts with one or two molecules of 2-mercaptoethanol are formed. Replacement of 2-mercaptoethanol by dithiothreitol gave 162 mg of enzyme from 36 l of culture yielding no clusters with the reducing agent.
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recombinant recombinant GST-tagged MurD from Escherichia coli by glutathione affinity chromatography, His-tagged MurD from Mycobacterium smegmatis by nickel affinity chromatography
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method that includes chromatography by a Talon resin
P0A091
recombinant protein
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Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expressed in Escherichia coli
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expressed in Escherichia coli JM83(pMLD58)
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gene murD, murD is located in a cluster near the other cell division genes such as ftsW, co-expression of GST-tagged MurD with MBP-fusion PknA, a mycobacterial eukaryotic-type serine/threonine kinase, in Escherichia coli BL21(DE3) cells leading to phosphorylation of mMurD. Also overexpression of murD in Mycobacterium smegmatis as His-tagged protein yields a phosphorylated enzyme
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expressed as His-tagged enzyme in Escherichia coli BL21 DE3/pLysS
P0A091
expression in Escherichia coli
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expressed as His-tagged enzyme in Escherichia coli BL21 DE3/pLysS
Staphylococcus pyogenes
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ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
D317A
-
reduced enzymatic activity with respect to the wild-type
D35A
-
reduced enzymatic activity with respect to the wild-type
E157A
-
reduced enzymatic activity with respect to the wild-type
E157K
-
reduced enzymatic activity with respect to the wild-type
H183A
-
reduced enzymatic activity with respect to the wild-type
H301A
-
reduced enzymatic activity with respect to the wild-type
K115A
-
reduced enzymatic activity with respect to the wild-type
K198A
-
reduced enzymatic activity with respect to the wild-type
K198F
-
reduced enzymatic activity with respect to the wild-type
N268A
-
reduced enzymatic activity with respect to the wild-type
N271A
-
reduced enzymatic activity with respect to the wild-type
R302A
-
reduced enzymatic activity with respect to the wild-type
R425A
-
reduced enzymatic activity with respect to the wild-type
Y194F
-
reduced enzymatic activity with respect to the wild-type
D35A
Escherichia coli DH5alpha
-
reduced enzymatic activity with respect to the wild-type
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E157A
Escherichia coli DH5alpha
-
reduced enzymatic activity with respect to the wild-type
-
E157K
Escherichia coli DH5alpha
-
reduced enzymatic activity with respect to the wild-type
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K115A
Escherichia coli DH5alpha
-
reduced enzymatic activity with respect to the wild-type
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Y194F
Escherichia coli DH5alpha
-
reduced enzymatic activity with respect to the wild-type
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TOF-123
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mutant enzyme TOF-95 is almost indistinguishable from wild type, glutamate-adding activity of mutant enzyme TOF-9 is about 17% of wild-type at 30 C and less at 43 C, no glutamate-adding activity can be detected in TOF-123 mutant enzyme, activity of mutant enzyme TOF-1 is marginally reduced to about 85% of wild type
TOF-9
-
mutant enzyme TOF-95 is almost indistinguishable from wild type, glutamate-adding activity of mutant enzyme TOF-9 is about 17% of wild-type at 30 C and less at 43 C, no glutamate-adding activity can be detected in TOF-123 mutant enzyme, activity of mutant enzyme TOF-1 is marginally reduced to about 85% of wild type
TOF-95
-
mutant enzyme TOF-95 is almost indistinguishable from wild type, glutamate-adding activity of mutant enzyme TOF-9 is about 17% of wild-type at 30 C and less at 43 C, no glutamate-adding activity can be detected in TOF-123 mutant enzyme, activity of mutant enzyme TOF-1 is marginally reduced to about 85% of wild type
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
analysis
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assay for monitoring enzyme activity based on the accumulation of adenosine 5'-diphosphate, a product of the reaction catalyzed by MurD ligase, by conversion to a fluorescent signal via a coupled enzyme system, with counterscreen assay to eliminate false positive results
drug development
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MurD is a target for small molecule chemotherapeutics