Information on EC 6.3.2.7 - UDP-N-acetylmuramoyl-L-alanyl-D-glutamate-L-lysine ligase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
6.3.2.7
-
RECOMMENDED NAME
GeneOntology No.
UDP-N-acetylmuramoyl-L-alanyl-D-glutamate-L-lysine ligase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-D-glutamate + L-lysine = ADP + phosphate + UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-gamma-D-glutamyl-L-lysine
show the reaction diagram
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-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
carboxamide formation
-
-
-
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carboxylic acid amide formation
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Metabolic pathways
-
-
Peptidoglycan biosynthesis
-
-
UDP-N-acetylmuramoyl-pentapeptide biosynthesis II (lysine-containing)
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peptidoglycan biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
UDP-N-acetylmuramoyl-L-alanyl-D-glutamate:L-lysine gamma-ligase (ADP-forming)
Involved in the synthesis of a cell-wall peptide in bacteria. This enzyme adds lysine in some Gram-positive organisms; in others and in Gram-negative organisms EC 6.3.2.13 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate---2,6-diaminopimelate ligase) adds 2,6-diaminopimelate instead.
CAS REGISTRY NUMBER
COMMENTARY hide
9023-51-2
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
the enzyme is involved in peptidoglycan biosynthesis and cell wall assembly
additional information
ATP-binding site structure and homology, overview. Asn407 makes a series of structurally important hydrogen bond interactions within the context of the architecture of the active site region
SUBSTRATE
PRODUCT                       
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-D-Glu + L-Lys
?
show the reaction diagram
-
one step in the biosynthesis of bacterial cell walls
-
-
-
ATP + UDP-N-acetylmuramoyl-L-Ala-D-Glu + L-Lys
ADP + phosphate + UDP-N-acetylmuramoyl-L-Ala-D-Glu-L-Lys
show the reaction diagram
ATP + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate + L-lysine
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysine
show the reaction diagram
additional information
?
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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-D-Glu + L-Lys
?
show the reaction diagram
-
one step in the biosynthesis of bacterial cell walls
-
-
-
ATP + UDP-N-acetylmuramoyl-L-alanyl-D-glutamate + L-lysine
ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysine
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cl-
-
activation by different anions in decreasing order: HPO42-, Cl-, SO42- , potassium salts give higher activity than the corresponding sodium salts
HPO42-
-
activation by different anions in decreasing order: HPO42-, Cl-, SO42- , potassium salts give higher activity than the corresponding sodium salts
Mn2+
-
Mn2+ or Mg2+ required, optimal concentration: 2 mM
phosphate
-
the presence of phosphate changes the enzyme conformation to a catalytically more active form
SO42-
-
activation by different anions in decreasing order: HPO42-, Cl-, SO42- , potassium salts give higher activity than the corresponding sodium salts
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2R)-2-amino-6-([[(3R)-3-carboxy-3-([N-[6-(phosphonooxy)hexanoyl]-L-alanyl]amino)propyl](hydroxy)phosphoryl]methyl)heptanedioic acid
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-
(2R)-2-amino-6-([[(3R)-3-carboxy-3-[[N-(6-[[[[[[(2R,5S)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl]methoxy](hydroxy)phosphoryl]oxy](hydroxy)phosphoryl]oxy]hexanoyl)-L-alanyl]amino]propyl](hydroxy)phosphoryl]methyl)heptanedioic acid
-
-
(6S,9R,14S)-benzyl 9-benzyloxycarbonyl-14-(4-benzyloxycarbonylaminobutyl)-2,2,6-trimethyl-4,7-dioxo-3-oxa-5,8,13-triazapentadecan-15-oate
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(R)-2-[bis(tert-butoxycarbonyl)amino]-5-oxopentanoate
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(R)-benzyl 2-[(tert-butoxycarbonyl)amino]-5-[methoxy(methyl)amino]-5-oxopentanoate
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(R)-benzyl 2-[bis(tert-butoxycarbonyl)amino]-5-[methoxy(methyl)amino]-5-oxopentanoate
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(S)-1-(2-tert-butoxycarbonylaminopropanoyl)piperidine-4-carboxylic acid
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(S)-6-amino-2-((R)-4-amino-4-carboxybutylamino)hexanoic acid
-
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(S)-6-amino-2-(piperidine-4-carboxamido)hexanoic acid
-
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(S)-6-amino-2-([[1-((S)-2-aminopropanoyl)piperidin-4-yl]methyl]amino)hexanoic acid
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(S)-6-amino-2-[(piperidin-4-ylmethyl)amino]hexanoic acid
-
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(S)-6-amino-2-[1-((S)-2-aminopropanoyl)piperidine-4-carboxamido]hexanoic acid 2,2,2-trifluoroacetate
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(S)-6-amino-2-[1-(carboxymethyl)piperidine-4-carboxamido]hexanoic acid
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(S)-6-amino-2-[[(R)-4-((S)-2-aminopropanamido)-4-carboxybutyl]amino]hexanoic acid
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(S)-benzyl 1-(2-tert-butoxycarbonylaminopropanoyl)piperidine-4-carboxylate
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(S)-benzyl 2-([(R)-5-(benzyloxy)-4-[bis(tert-butoxycarbonyl)amino]-5-oxopentyl]amino)-6-benzyloxycarbonylaminohexanoate
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(S)-benzyl 6-benzyloxycarbonylamino-2-[([1-[(S)-2-(tert-butoxycarbonylamino)propanoyl]piperidin-4-yl]methyl)amino]hexanoate
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(S)-benzyl 6-benzyloxycarbonylamino-2-[1-((S)-2-tertbutoxycarbonylaminopropanoyl)piperidine-4-carboxamido]hexanoate
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(S)-benzyl 6-benzyloxycarbonylamino-2-[1-(2-tertbutoxy-2-oxoethyl)piperidine-4-carboxamido]hexanoate
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(S)-N-(2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)piperidine-4-carboxamide
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(S)-tert-butyl 4-[(1-benzyloxy-6-benzyloxycarbonylamino-1-oxohexan-2-yl)carbamoyl]piperidine-1-carboxylate
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(S)-tert-butyl 4-[[(1-benzyloxy-6-benzyloxycarbonylamino-1-oxohexan-2-yl)amino]methyl]piperidine-1-carboxylate
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1-(2-tert-butoxy-2-oxoethyl)piperidine-4-carboxylic acid
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2-([hydroxy[1-([N-[(4-nitrobenzyl)sulfonyl]-D-alanyl]amino)ethyl]phosphoryl]methyl)pentanedioic acid
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1 mM, 13% residual activity
2-[[(1-[[(2E)-3-(1,3-benzodioxol-5-yl)prop-2-enoyl]amino]ethyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
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1 mM, 52% residual activity
2-[[(1-[[(benzyloxy)carbonyl]amino]ethyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
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1 mM, 35% residual activity
2-[[hydroxy(1-[[(2E)-3-(3-hydroxyphenyl)prop-2-enoyl]amino]ethyl)phosphoryl]methyl]pentanedioic acid
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1 mM, 21% residual activity
2-[[hydroxy(1-[[(2E)-3-phenylprop-2-enoyl]amino]ethyl)phosphoryl]methyl]pentanedioic acid
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1 mM, 50% residual activity
2-[[hydroxy(1-[[(3-nitrobenzyl)sulfonyl]amino]ethyl)phosphoryl]methyl]pentanedioic acid
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1 mM, 52% residual activity
2-[[hydroxy(1-[[(3-nitrophenyl)sulfonyl]amino]ethyl)phosphoryl]methyl]pentanedioic acid
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1 mM, 39% residual activity
2-[[hydroxy(1-[[(4-nitrobenzyl)sulfonyl]amino]ethyl)phosphoryl]methyl]pentanedioic acid
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1 mM, 44% residual activity
2-[[hydroxy(2-methyl-1-[[(3-nitrobenzyl)sulfonyl]-amino]butyl)phosphoryl]methyl]pentanedioic acid
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1 mM, 71% residual activity
2-[[hydroxy(2-methyl-1-[[(4-nitrobenzyl)sulfonyl]-amino]butyl)phosphoryl]methyl] pentanedioic acid
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1 mM, 54% residual activity
2-[[hydroxy(2-methyl-1-[[(4-nitrobenzyl)sulfonyl]amino]propyl)phosphoryl]methyl] pentanedioic acid
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1 mM, 29% residual activity
2-[[[1-[(1,3-benzodioxol-5-ylacetyl)amino]ethyl](hydroxy)phosphoryl]methyl]pentanedioic acid
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1 mM, 12% residual activity; 1 mM, 42% residual activity; 1 mM, 60% residual activity
3-[(1-[[(benzyloxy)carbonyl]amino]ethyl)(hydroxy)phosphoryl]propanoic acid
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1 mM, 50% residual activity
3-[hydroxy[1-([N-[(4-nitrobenzyl)sulfonyl]-D-alanyl]amino)ethyl]phosphoryl]propanoic acid
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1 mM, 46% residual activity
3-[[1-[(1,3-benzodioxol-5-ylacetyl)amino]ethyl](hydroxy)phosphoryl]propanoic acid
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1 mM, 35% residual activity
4-benzyloxycarbonylpiperidin-1-ium 4-methylbenzenesulfonate
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ATP
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above 10 mM
benzyl 1-(2-tert-butoxy-2-oxoethyl)piperidine-4-carboxylate
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N-[(S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl]-1-[(S)-2-aminopropanoyl]piperidine-4-carboxamide
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tert-butyl 4-formylpiperidine-1-carboxylate
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tert-butyl 4-[(2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)carbamoyl]piperidine-1-carboxylate
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tert-butyl 4-[methoxy(methyl)carbamoyl]piperidine-1-carboxylate
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tert-butyl [(S)-1-[4-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-ylcarbamoyl)piperidin-1-yl]-1-oxopropan-2-yl]carbamate
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UDP-N-acetylmuramoyl-L-Ala-D-Glu
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above 10 mM
additional information
-
design and synthesise a small focused library of peptidomimetics as potential inhibitors of MurE from Staphylococcus aureus, overview
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
isopropyl-beta-D-thiogalactosylpyranoside
-
concentration 1mM
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.125 - 0.55
ATP
0.0205 - 0.55
L-Lys
0.55 - 20
L-lysine
0.37 - 0.49
Lys
0.087 - 0.59
UDP-N-acetylmuramoyl-L-Ala-D-Glu
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
9
ATP
Streptococcus pyogenes
-
23C
9
L-Lys
Streptococcus pyogenes
-
23C
0.001 - 4.833
L-lysine
9
UDP-N-acetylmuramoyl-L-Ala-D-Glu
Streptococcus pyogenes
-
23C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.001 - 8.787
L-lysine
134
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.7
(2R)-2-amino-6-([[(3R)-3-carboxy-3-([N-[6-(phosphonooxy)hexanoyl]-L-alanyl]amino)propyl](hydroxy)phosphoryl]methyl)heptanedioic acid
Staphylococcus aureus
-
pH and temperature not specified in the publication
0.0011
(2R)-2-amino-6-([[(3R)-3-carboxy-3-[[N-(6-[[[[[[(2R,5S)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl]methoxy](hydroxy)phosphoryl]oxy](hydroxy)phosphoryl]oxy]hexanoyl)-L-alanyl]amino]propyl](hydroxy)phosphoryl]methyl)heptanedioic acid
Staphylococcus aureus
-
pH and temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.07
-
noninduced cells
23.4
-
cells induced with isopropyl-beta-D-thiogalactosylpyranoside
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8 - 8.5
-
activity decreases sharply below pH 8.0, optimal activity at pH 8.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
15 - 40
-
15C: about 30% of maximal activity, 40C: about 45% of maximal activity
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.02
-
calculation from amino acid sequence
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Staphylococcus aureus (strain NCTC 8325)
Staphylococcus aureus (strain NCTC 8325)
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purified recombinant His-tagged enzyme in complex with UDP-MurNAc-Ala-Glu-Lys or with UDP-MurNAc-Ala-Glu-Lys and ADP, from 0.1 M Na-HEPES/MOPS, pH 7.5, 0.09 M nitrate phosphate sulfate mix, 30% w/v PEG550MME/PEG20K, method evaluation, X-ray diffraction structure determination and analysis at 1.8-1.9 A resolution, molecular replacement
crystals are obtained by the hanging-drop vapour-diffusion method at 291 K from solutions containing 25%(w/v) polyethylene glycol 2000 monomethylether, 0.2 M potassium thiocyanate, 0.1 M MES pH 6.5 in the presence of uridine 5'-diphospho-N-acetylmuramoyl alanyl glutamate (UDP-MurNAc-l-Ala-d-Glu) with and without 5'-adenylyl imidophosphate (AMP-PNP), a non-hydrolysable analogue of ATP. Crystals grown in the presence of two ligands belong to space group P1, with unit-cell parameters a = 68.4 A, b = 71.4 A, c = 74.8 A, alpha = 73.4, beta = 80.5, gamma = 72.3 A. Crystals grown in the presence of UDP-MurNAc-l-Ala-d-Glu alone belong to space group P2(1), with unit-cell parameters a = 71.1 A, b = 129.4 A, c = 74.6 A, beta = 106.3
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
-
rapid loss of activity at or below, even at 0C
1270
8
-
stable at
1270
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, stable for over 3 months when stored in the lyophilized form
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombiant His-tagged enzyme from Escherichia coli strain BL21(DE3):pLysS by nickel affinity chromatography, gel filtration, and ion exchange chromatography
recombinant protein
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloned into the high-expression plasmid pET21b and overexpressed in Escherichia coli BL21 (DE3) Star
-
expressed as a glutathione-S-transferase/His12 fusion in Escherichia coli
-
expressed in Escherichia coli. Overexpression induced with isopropyl-beta-D-thiogalactosylpyranoside results in abnormal morphological changes and subsequent cell lysis
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expression in Escherichia coli
-
gene murE, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3):pLysS from plasmid pET2160:murESa, coexpression with chaperone from pREP4groESL
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A409R
site-directed mutagenesis, the lytic phenotype observed upon overexpression of the wild-type murESa gene is replicated with the mutant
D406A
site-directed mutagenesis, the mutant shows very low or no activity in vivo
E460A
site-directed mutagenesis, the mutant shows very low or no activity in vivo
N407A
site-directed mutagenesis, inactive mutant
N407R
site-directed mutagenesis, the growth curve of N407R mutant is similar to that of wild-type murESa
P408A
site-directed mutagenesis, the lytic phenotype observed upon overexpression of the wild-type murESa gene is replicated with the mutant
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