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 hide
6.3.2.9
-
RECOMMENDED NAME
GeneOntology No.
UDP-N-acetylmuramoyl-L-alanine-D-glutamate ligase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + UDP-N-acetyl-alpha-D-muramoyl-L-alanine + D-glutamate = ADP + phosphate + UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-D-glutamate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
carboxamide formation
-
-
-
-
carboxylic acid amide formation
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
D-Glutamine and D-glutamate metabolism
-
-
Metabolic pathways
-
-
peptidoglycan biosynthesis
-
-
Peptidoglycan biosynthesis
-
-
UDP-N-acetylmuramoyl-pentapeptide biosynthesis I (meso-diaminopimelate containing)
-
-
UDP-N-acetylmuramoyl-pentapeptide biosynthesis II (lysine-containing)
-
-
SYSTEMATIC NAME
IUBMB Comments
UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase (ADP-forming)
Involved in the synthesis of a cell-wall peptide in bacteria.
CAS REGISTRY NUMBER
COMMENTARY hide
9023-59-0
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
168
-
-
Manually annotated by BRENDA team
168
-
-
Manually annotated by BRENDA team
Escherichia coli DH5-alpha
strain DH5alpha
-
-
Manually annotated by BRENDA team
K12
-
-
Manually annotated by BRENDA team
9602
-
-
Manually annotated by BRENDA team
9602
-
-
Manually annotated by BRENDA team
strain H37Ra, gene m-murD or Rv2155c
SwissProt
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
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
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
ATP + dihydrouridine 5'-diphosphate-N-acetylmuramoyl-L-Ala + Glu
ADP + phosphate + dihydrouridine 5'-diphosphate-N-acetylmuramoyl-L-Ala-D-Glu
show the reaction diagram
ATP + UDP-N-acetylmuramate-L-alanine
adenosine 5'-tetraphosphate
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
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 + DL-homocysteic acid
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-DL-homocysteic acid
show the reaction diagram
-
-
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala + 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-acetylmuramyl-L-alanine + D-glutamate
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate
show the reaction diagram
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
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + UDP-N-acetylmuramoyl-L-Ala + Glu
?
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
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
arsenate
-
increases storage stability
Ca2+
-
increases storage stability
Cd2+
-
abolishes the enzyme activity at 5mM
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
COMMENTARY hide
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
(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-Asp
-
weak
D-erythro-3-Methylglutamic acid
-
-
D-erythro-4-Methylglutamic acid
-
-
D-Gln
-
weak
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
-
-
HLPTSSLFDTTG
-
-
HSSWYIQHFPPL
-
i.e. peptide MD-12, inhibits MurD
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
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.2
1-phospho-N-acetylmuramoyl-L-Ala
-
-
0.03 - 5.4
ATP
0.055 - 0.28
D-Glu
0.044 - 5.16
D-glutamate
0.01
dihydrouridine 5'-diphosphate-N-acetylmuramoyl-L-Ala
-
-
0.138
MgATP2-
-
-
0.0073
UDP-N-acetylmuramate-L-alanine
-
37C
0.012 - 0.304
UDP-N-acetylmuramoyl L-alanine
0.16
UDP-N-acetylmuramoyl-Ala
-
-
0.0055 - 0.041
UDP-N-acetylmuramoyl-L-Ala
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0003 - 6.08
D-glutamate
additional information
additional information
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
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 - 1.66
N-(6-butoxy-naphthalene-2-sulfonyl)-D-glutamic acid
0.87 - 2.13
N-(6-butoxy-naphthalene-2-sulfonyl)-L-glutamic acid
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.089
(2R)-2-[((3-[(Z)-(4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]phenyl)carbonyl)amino]pentanedioic acid
Escherichia coli
-
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
Escherichia coli
-
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
Escherichia coli
-
-
0.132
(2R)-2-[[(7-(3-phenylpropoxy)naphthalen-2-yl)sulfonyl]amino]pentanedioic acid
Escherichia coli
-
-
0.105
(2R)-2-[[(7-(4-cyanobenzyloxy)naphthalen-2-yl)sulfonyl]amino]pentanedioic acid
Escherichia coli
-
-
0.239
(2R)-2-[[(7-benzyloxynaphthalen-2-yl)sulfonyl]amino]pentanedioic acid
Escherichia coli
-
-
0.18
(2R)-2-[[(7-butoxynaphthalen-2-yl)sulfonyl]amino]pentanedioic acid
Escherichia coli
-
-
0.17
(2R)-2-[[(7-pentoxynaphthalen-2-yl)sulfonyl]amino]pentanedioic acid
Escherichia coli
-
-
0.01
(2S)-2-[((4-[(Z)-(4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]phenyl)carbonyl)amino]pentanedioic acid
Escherichia coli
-
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
Escherichia coli
-
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
Escherichia coli
-
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
Escherichia coli
-
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
Escherichia coli
-
pH 8.0, 37C
0.045
(R,Z)-2-(3-((4-((4-oxo-2-thioxothiazolidin-5-ylidene)methyl)phenylamino)methyl)benzamido)pentanedioic acid
Escherichia coli
-
pH 8.0, 37C
0.01
2,3,4,5-tetrabromo-6-(3,6-dihydroxy-9H-xanthen-9-yl)benzoic acid
Escherichia coli
-
pH 8.0, 37C
0.074
2-([2-(2-naphthylsulfonyl)hydrazono)methyl]phenyl 4-nitrobenzenesulfonate
Escherichia coli
-
pH 8.0, 37C
0.055
2-bromo-N-(4-([2-(2-naphthylsulfonyl)hydrazono]methyl)phenyl)benzamide
Escherichia coli
-
pH 8.0, 37C
0.046
2-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]-5-hydroxybenzoic acid
Escherichia coli
-
pH 8.6, 37C
0.038
2-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]benzene-1,4-dicarboxylic acid
Escherichia coli
-
pH 8.6, 37C
0.105
3-([[(5-amino-1,3,4-thiadiazol-2-yl)sulfanyl]acetyl]amino)-4-methylbenzoic acid
Escherichia coli
-
37C
0.03
3-bromo-N-(4-([2-(2-naphthylsulfonyl)hydrazono]methyl)phenyl)benzamide
Escherichia coli
-
pH 8.0, 37C
0.0084
4-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]benzene-1,3-dicarboxylic acid
Escherichia coli
-
pH 8.6, 37C
0.182
4-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]cyclohexane-1,3-dicarboxylic acid
Escherichia coli
-
pH 8.6, 37C
0.177
beta,gamma-methyleneadenosine 5'-triphosphate
Escherichia coli
-
37C
1.5
CPAHWPHPC
Escherichia coli
-
pH 8.0, 37C
0.62
CSAWSNKFC
Escherichia coli
-
pH 8.0, 37C
0.14
HSSWYIQHFPPL
Escherichia coli
-
pH 8.0, 37C
0.07
N'-((2-[(2-nitrobenzyl)oxy]phenyl)methylidene)-2-naphthalenesulfonohydrazide
Escherichia coli
-
pH 8.0, 37C
0.062
N'-((2-[(4-cyanobenzyl)oxy]phenyl)methylidene)-2-naphthalenesulfonohydrazide
Escherichia coli
-
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
Escherichia coli
-
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
Escherichia coli
-
pH 8.0, 37C
0.28
N-(6-butoxy-naphthalene-2-sulfonyl)-D-glutamic acid
Escherichia coli
-
-
0.71
N-(6-butoxy-naphthalene-2-sulfonyl)-L-glutamic acid
Escherichia coli
-
-
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
Escherichia coli
-
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
Pseudomonas aeruginosa
-
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
additional information
additional information
Pseudomonas aeruginosa
-
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]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.261
-
Escherichia coli JM83(pDML13)
1.772
-
37C
1.92
-
Escherichia coli JM83 (pMLD50)
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8.4 - 8.8
-
-
8.9 - 9.2
-
-
9.4 - 10.5
-
enzyme from spores
9.5 - 10.5
-
enzyme from vegetative cells
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
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)
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
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
46840
-
mass spectrometry
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
COMMENTARY hide
LITERATURE
phosphoprotein
the mycobacterial eukaryotic-type serine/threonine kinase PknA transphosphorylates MurD
Crystallization/COMMENTARY
ORGANISM
UNIPROT
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
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
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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
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moelcular docking of inhibitor 6_3_2-9_4-R16
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structure of MurD in complex with (R,Z)-2-(3-((4-((2,4-dioxothiazolidin-5-ylidene)methyl)phenylamino)methyl)benzamido)pentanedioic acid
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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
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generation of MurD 3D models using crystal structures of PDB entries 1EEH and 2JFF as templates in Modeller9v7
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-18C, 20-30% loss of activity
-
-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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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
method that includes chromatography by a Talon resin
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 protein
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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
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed as His-tagged enzyme in Escherichia coli BL21 DE3/pLysS
expressed in Escherichia coli
-
expressed in Escherichia coli JM83(pMLD58)
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expression in Escherichia coli
-
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
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
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 DH5-alpha
-
reduced enzymatic activity with respect to the wild-type
-
E157A
Escherichia coli DH5-alpha
-
reduced enzymatic activity with respect to the wild-type
-
E157K
Escherichia coli DH5-alpha
-
reduced enzymatic activity with respect to the wild-type
-
K115A
Escherichia coli DH5-alpha
-
reduced enzymatic activity with respect to the wild-type
-
Y194F
Escherichia coli DH5-alpha
-
reduced enzymatic activity with respect to the wild-type
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TOF-123
-
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
COMMENTARY hide
LITERATURE
analysis
-
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
-
MurD is a target for small molecule chemotherapeutics
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