Information on EC 2.5.1.7 - UDP-N-acetylglucosamine 1-carboxyvinyltransferase

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The expected taxonomic range for this enzyme is: Bacteria

EC NUMBER
COMMENTARY
2.5.1.7
-
RECOMMENDED NAME
GeneOntology No.
UDP-N-acetylglucosamine 1-carboxyvinyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
phosphoenolpyruvate + UDP-N-acetyl-alpha-D-glucosamine = phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-alpha-D-glucosamine
show the reaction diagram
mechanism, formation of a covalent intermediate between enzyme and enolpyruvate moiety
-
phosphoenolpyruvate + UDP-N-acetyl-alpha-D-glucosamine = phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-alpha-D-glucosamine
show the reaction diagram
active site SH-group
-
phosphoenolpyruvate + UDP-N-acetyl-alpha-D-glucosamine = phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-alpha-D-glucosamine
show the reaction diagram
the addition step proceeds with protonation of C-3 of phosphoenolpyruvate from the 2-si face
-
phosphoenolpyruvate + UDP-N-acetyl-alpha-D-glucosamine = phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-alpha-D-glucosamine
show the reaction diagram
mechanism
-
phosphoenolpyruvate + UDP-N-acetyl-alpha-D-glucosamine = phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-alpha-D-glucosamine
show the reaction diagram
Cys115 is the active site nucleophile
-
phosphoenolpyruvate + UDP-N-acetyl-alpha-D-glucosamine = phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-alpha-D-glucosamine
show the reaction diagram
Cys115 is the active site nucleophile
-
phosphoenolpyruvate + UDP-N-acetyl-alpha-D-glucosamine = phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-alpha-D-glucosamine
show the reaction diagram
structure analysis of conformational changes upon substrate binding
-
phosphoenolpyruvate + UDP-N-acetyl-alpha-D-glucosamine = phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-alpha-D-glucosamine
show the reaction diagram
enyme exhibits an open conformation when substrate-free, and a closed, tightly-packed conformation upon substrate binding; mechanism
-
phosphoenolpyruvate + UDP-N-acetyl-alpha-D-glucosamine = phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-alpha-D-glucosamine
show the reaction diagram
Lys22 is located near the active site and involved in substrate binding
-
phosphoenolpyruvate + UDP-N-acetyl-alpha-D-glucosamine = phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-alpha-D-glucosamine
show the reaction diagram
Cys115 in the active site can act as proton donor, necessary for activity, or as a nucleophile; mechanism
-
phosphoenolpyruvate + UDP-N-acetyl-alpha-D-glucosamine = phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-alpha-D-glucosamine
show the reaction diagram
thermodynamical investigation of substrate binding and binding of inhibitory substrate analogue fosfomycin
P33038
phosphoenolpyruvate + UDP-N-acetyl-alpha-D-glucosamine = phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-alpha-D-glucosamine
show the reaction diagram
Asn23 and Asp305 are essential in the active site; D305 has a dual role as a general base and an essential binding partner to UDP-GlcNAc; enyme exhibits an open conformation when substrate-free, and a closed, tightly-packed conformation upon substrate binding; mechanism; N23 is responsible for stabilization of transition states
-
phosphoenolpyruvate + UDP-N-acetyl-alpha-D-glucosamine = phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-alpha-D-glucosamine
show the reaction diagram
exchange of cysteine to aspartate in the active site
-
phosphoenolpyruvate + UDP-N-acetyl-alpha-D-glucosamine = phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-alpha-D-glucosamine
show the reaction diagram
intramolecular general acid catalysis through protonation of the bridging oxygen of the phosphate
-
phosphoenolpyruvate + UDP-N-acetyl-alpha-D-glucosamine = phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-alpha-D-glucosamine
show the reaction diagram
tetrahedral reaction intermediate, overall addition-elimination reaction is halted after the addition step
-
phosphoenolpyruvate + UDP-N-acetyl-alpha-D-glucosamine = phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-alpha-D-glucosamine
show the reaction diagram
exchange of cysteine to aspartate in the active site
Chlamydia trachomatis MurA
-
-
phosphoenolpyruvate + UDP-N-acetyl-alpha-D-glucosamine = phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-alpha-D-glucosamine
show the reaction diagram
Asn23 and Asp305 are essential in the active site; Cys115 in the active site can act as proton donor, necessary for activity, or as a nucleophile; D305 has a dual role as a general base and an essential binding partner to UDP-GlcNAc; enyme exhibits an open conformation when substrate-free, and a closed, tightly-packed conformation upon substrate binding; mechanism; mechanism; N23 is responsible for stabilization of transition states; structure analysis of conformational changes upon substrate binding
Enterobacter cloacae MurA
-
-
phosphoenolpyruvate + UDP-N-acetyl-alpha-D-glucosamine = phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-alpha-D-glucosamine
show the reaction diagram
Cys115 is the active site nucleophile
Escherichia coli MurA
-
-
phosphoenolpyruvate + UDP-N-acetyl-alpha-D-glucosamine = phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-alpha-D-glucosamine
show the reaction diagram
mechanism; the addition step proceeds with protonation of C-3 of phosphoenolpyruvate from the 2-si face
Escherichia coli MurZ
-
-
phosphoenolpyruvate + UDP-N-acetyl-alpha-D-glucosamine = phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-alpha-D-glucosamine
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
carboxyvinyl group transfer
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Amino sugar and nucleotide sugar 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
phosphoenolpyruvate:UDP-N-acetyl-D-glucosamine 1-carboxyvinyltransferase
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
enol-pyruvyltransferase
-
-
enol-pyruvyltransferase
Enterobacter cloacae DSM 30054
-
-
-
enolpyruvyl UDP-GlcNAc synthase
-
-
enoylpyruvate transferase
-
-
-
-
enoylpyruvatetransferase
-
-
-
-
MurA
B5F9P4
-
MurA
B6DVJ7
-
MurA
Aliivibrio fischeri MJ11
B5F9P4
-
-
MurA
-
recombinant enzyme
MurA
P0A749
-
MurA
Escherichia coli JM109
-
-
-
MurA
Q49K92
-
MurA
Staphylococcus aureus SH1000
-
-
-
MurA transferase
-
-
-
-
phosphoenolpyruvate-UDP-acetylglucosamine-3-enolpyruvyltransferase
-
-
-
-
phosphoenolpyruvate:UDP-2-acetamido-2-deoxy-D-glucose 2-enoyl-1-carboxyethyltransferase
-
-
-
-
phosphoenolpyruvate:uridine diphosphate N-acetylglucosamine enolpyruvyltransferase
-
-
-
-
phosphoenolpyruvate:uridine-5'-diphospho-N-acetyl-2-amino-2-deoxyglucose-3-enolpyruvyltransferase
-
-
-
-
phosphopyruvate-uridine diphosphoacetylglucosamine pyruvatetransferase
-
-
-
-
pyruvate-UDP-acetylglucosamine transferase
-
-
-
-
pyruvate-uridine diphospho-N-acetyl-glucosamine transferase
-
-
-
-
pyruvate-uridine diphospho-N-acetylglucosamine transferase
-
-
-
-
pyruvatetransferase, phosphoenolpyruvate-uridine diphosphoacetylglucosamine
-
-
-
-
pyruvic-uridine diphospho-N-acetylglucosaminyltransferase
-
-
-
-
UDP-GlcNAc enolpyruvyl transferase
-
-
UDP-GlcNAc enolpyruvyl transferase
-
-
UDP-GlcNAc enolpyruvyl transferase
Escherichia coli MurA, Escherichia coli MurZ
-
-
-
UDP-GlcNAc enolpyruvyl transferase
-
-
UDP-N-acetylglucosamine 1-carboxyvinyl transferase
-
-
UDP-N-acetylglucosamine 1-carboxyvinyl-transferase
-
-
-
-
UDP-N-acetylglucosamine 1-carboxyvinyltransferase
P33038
-
UDP-N-acetylglucosamine enolpyruvyl transferase
B5F9P4
-
UDP-N-acetylglucosamine enolpyruvyl transferase
B6DVJ7
-
UDP-N-acetylglucosamine enolpyruvyl transferase
Aliivibrio fischeri MJ11
B5F9P4
-
-
UDP-N-acetylglucosamine enolpyruvyl transferase
-
-
UDP-N-acetylglucosamine enolpyruvyl transferase
P33038
-
UDP-N-acetylglucosamine enolpyruvyl transferase
-
-
UDP-N-acetylglucosamine enolpyruvyl transferase
P0A749
-
UDP-N-acetylglucosamine enolpyruvyl transferase
Escherichia coli JM109
-
-
-
UDP-N-acetylglucosamine enolpyruvyl transferase
-
-
UDP-N-acetylglucosamine enolpyruvyl transferase
P45025
-
UDP-N-acetylglucosamine enolpyruvyl transferase
P0A5L2
-
UDP-N-acetylglucosamine enolpyruvyl transferase
-
-
UDP-N-acetylglucosamine enolpyruvyl transferase
Q49K92
-
UDP-N-acetylglucosamine enolpyruvyl transferase
-
-
UDP-N-acetylglucosamine enolpyruvyl transferase
Staphylococcus aureus SH1000
-
-
-
UDP-N-acetylglucosamine enolpyruvyl transferase
-
-
UDP-N-acetylglucosamine enolpyruvyl transferase
H2DMJ3
-
UDP-N-acetylglucosamine enolpyruvyl transferase
Q8GNY2
-
UDP-N-acetylglucosamine enolpyruvyltransferase
-
-
UDP-N-acetylglucosamine enolpyruvyltransferase
Enterobacter cloacae MurA
-
-
-
UDP-N-acetylglucosamine enoylpyruvyltransferase
-
-
-
-
UDP-NAG enolpyruvyl transferase
P0A5L2
-
UNAG enolpyruvyl transferase
-
-
additional information
-
phylogenetic tree
CAS REGISTRY NUMBER
COMMENTARY
9023-27-2
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
Aliivibrio fischeri MJ11
-
SwissProt
Manually annotated by BRENDA team
isoforms MurA1, murA2
-
-
Manually annotated by BRENDA team
strain T
-
-
Manually annotated by BRENDA team
Bacillus cereus T
strain T
-
-
Manually annotated by BRENDA team
gene murA; MurA; serovar L2
-
-
Manually annotated by BRENDA team
Chlamydia trachomatis MurA
MurA
-
-
Manually annotated by BRENDA team
MurA; recombinant purified enzyme
-
-
Manually annotated by BRENDA team
MurA; recombinant purified enzyme
Uniprot
Manually annotated by BRENDA team
strain NRC 492
-
-
Manually annotated by BRENDA team
Enterobacter cloacae DSM 30054
Nr. 30054
-
-
Manually annotated by BRENDA team
Enterobacter cloacae MurA
MurA
-
-
Manually annotated by BRENDA team
Enterobacter cloacae MurA
MurA
Uniprot
Manually annotated by BRENDA team
Enterobacter cloacae NRC 492
strain NRC 492
-
-
Manually annotated by BRENDA team
gene murA
-
-
Manually annotated by BRENDA team
gene murZ, at 69.3 min of the chromosome
SwissProt
Manually annotated by BRENDA team
gene murZ; MurZ
-
-
Manually annotated by BRENDA team
K-12 strain KMBL-146; strain K-235
-
-
Manually annotated by BRENDA team
K-12; MurA
-
-
Manually annotated by BRENDA team
murA instead of murZ is recommended to be used to designate the gene at 69.3 min of the chromosome
SwissProt
Manually annotated by BRENDA team
Escherichia coli JM109
-
-
-
Manually annotated by BRENDA team
Escherichia coli K-235
strain K-235
-
-
Manually annotated by BRENDA team
Escherichia coli MurA
MurA
-
-
Manually annotated by BRENDA team
Escherichia coli MurZ
MurZ
-
-
Manually annotated by BRENDA team
strain ATCC VR1471
TrEMBL
Manually annotated by BRENDA team
Staphylococcus aureus SH1000
-
-
-
Manually annotated by BRENDA team
strain Texas 26
-
-
Manually annotated by BRENDA team
Staphylococcus epidermidis Texas 26
strain Texas 26
-
-
Manually annotated by BRENDA team
2 genes murA1 and murA2, 2 isoforms of enzyme MurA; strain R6
-
-
Manually annotated by BRENDA team
strain ATCC 1470
TrEMBL
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
gram-negative bacteria have only one copy of the murA gene, its deletion is lethal
malfunction
-
frame deletion of murAA leads to increased susceptibility of Enterococcus faecalis to the cephalosporins ceftriaxone and ceftazidime
physiological function
-, B6DVJ7
key enzyme is involved in bacterial cell wall peptidoglycan synthesis and a target for the antimicrobial agent fosfomycin, a structural analog of the MurA substrate phosphoenol pyruvate
physiological function
-
catalyzes the first committed step in peptidoglycan biosynthesis
physiological function
-
enzyme catalyzes the first step of bacterial cell wall synthesis
physiological function
-
enzyme catalyzes the first committed step of peptidoglycan biosynthesis
physiological function
-
enzyme catalyzes the first committed step of bacterial cell wall biosynthesis
physiological function
-
the enzyme is necessary but not sufficient for intrinsic cephalosporin resistance of Enterococcus faecalis
physiological function
-
the enzyme catalyzes the first committed step in the biosynthesis of peptidoglycan, an integral and essential component of the bacterial cell wall
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
phosphoenol-2-oxobutyrate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetylglucosaminyl-enol-2-oxobutyrate
show the reaction diagram
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
P33038
-
-
r
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
-
r
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
P33038
-
-
r
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
-
r
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
-
-
r
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-, P0A749
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
P0A749
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Q49K92, -
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Q8GNY2, -
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
i.e. UDP-N-acetyl-D-glucosamine-enolpyruvate
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
i.e. UDP-N-acetyl-D-glucosamine-enolpyruvate
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
i.e. UDP-N-acetyl-D-glucosamine-enolpyruvate
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
i.e. UDP-N-acetyl-D-glucosamine-enolpyruvate
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
i.e. UDP-N-acetyl-D-glucosamine-enolpyruvate
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
i.e. UDP-N-acetyl-D-glucosamine-enolpyruvate
r
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
i.e. UDP-N-acetyl-D-glucosamine-enolpyruvate
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
i.e. UDP-N-acetyl-D-glucosamine-enolpyruvate
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
specific for phosphoenolpyruvate and UDP-N-acetyl-D-glucosamine
i.e. UDP-N-acetyl-D-glucosamine-enolpyruvate
r
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
substrate binding structure
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
substrate binding structure
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
substrate binding structure, thermodynamic parameters of substrate binding, wild-type, C115S and K22 mutants
-
r
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
peptidoglycan formation is essential for progression through the developmental cycle as well as for cell division
-
-
-
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
enzyme activity is essential for the organism, the 2 isoforms can substitute for each other
-
-
-
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
enzyme catalyzes the first committed step in the biosynthesis of bacterial cell wall peptidoglycan
-
-
-
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
enzyme catalyzes the first committed step in the biosynthesis of bacterial cell wall peptidoglycan
-
-
-
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
pathway for biosynthesis of UDP-N-acetylmuramic acid
-
-
-
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
pathway for biosynthesis of UDP-N-acetylmuramic acid
-
-
-
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Enterobacter cloacae MurA
-
substrate binding structure
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Enterobacter cloacae MurA
-
-
-
r
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Enterobacter cloacae MurA
-
-
-
r
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Escherichia coli MurZ
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Escherichia coli MurZ
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Escherichia coli MurZ
-
enzyme catalyzes the first committed step in the biosynthesis of bacterial cell wall peptidoglycan
-
-
-
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Escherichia coli MurA
-
-
i.e. UDP-N-acetyl-D-glucosamine-enolpyruvate
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Escherichia coli MurA
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Enterobacter cloacae DSM 30054
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Enterobacter cloacae DSM 30054
-
enzyme catalyzes the first committed step in the biosynthesis of bacterial cell wall peptidoglycan
-
-
-
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Escherichia coli K-235
-
-
i.e. UDP-N-acetyl-D-glucosamine-enolpyruvate
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Escherichia coli K-235
-
pathway for biosynthesis of UDP-N-acetylmuramic acid
-
-
-
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Bacillus cereus T
-
-
i.e. UDP-N-acetyl-D-glucosamine-enolpyruvate
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Enterobacter cloacae NRC 492
-
specific for phosphoenolpyruvate and UDP-N-acetyl-D-glucosamine
i.e. UDP-N-acetyl-D-glucosamine-enolpyruvate
r
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Enterobacter cloacae NRC 492
-
pathway for biosynthesis of UDP-N-acetylmuramic acid
-
-
-
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Staphylococcus epidermidis Texas 26
-
-
i.e. UDP-N-acetyl-D-glucosamine-enolpyruvate
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Chlamydia trachomatis MurA
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Chlamydia trachomatis MurA
-
peptidoglycan formation is essential for progression through the developmental cycle as well as for cell division
-
-
-
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-, B6DVJ7
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine + phosphate
show the reaction diagram
-
-
-
-
r
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine + phosphate
show the reaction diagram
-
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine + phosphate
show the reaction diagram
-
-
-
-
r
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine + phosphate
show the reaction diagram
-
-
-
-
r
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine + phosphate
show the reaction diagram
-
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine + phosphate
show the reaction diagram
-
-
-
-
r
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine + phosphate
show the reaction diagram
-
-
-
-
r
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine + phosphate
show the reaction diagram
-
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine + phosphate
show the reaction diagram
P0A5L2
-
-
-
r
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine + phosphate
show the reaction diagram
-, B5F9P4
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine + phosphate
show the reaction diagram
Escherichia coli JM109
-
-
-
-
r
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine + phosphate
show the reaction diagram
Aliivibrio fischeri MJ11
B5F9P4
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine + phosphate
show the reaction diagram
Staphylococcus aureus SH1000
-
-
-
-
r
additional information
?
-
-
no activity with (Z)-phosphoenol-2-oxobutyrate, phosphoenol-3-bromopyruvate and phosphoenol-3-phenylpyruvate
-
-
-
additional information
?
-
-
MurA has also ATPase activity
-
-
-
additional information
?
-
-
the enzyme does not display appreciable catalytic activity with UDP-N-acetyl-D-galactosamine as a substrate
-
-
-
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
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
peptidoglycan formation is essential for progression through the developmental cycle as well as for cell division
-
-
-
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
enzyme activity is essential for the organism, the 2 isoforms can substitute for each other
-
-
-
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
enzyme catalyzes the first committed step in the biosynthesis of bacterial cell wall peptidoglycan
-
-
-
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
enzyme catalyzes the first committed step in the biosynthesis of bacterial cell wall peptidoglycan
-
-
-
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
pathway for biosynthesis of UDP-N-acetylmuramic acid
-
-
-
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
pathway for biosynthesis of UDP-N-acetylmuramic acid
-
-
-
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
-, B6DVJ7
-
-
-
?
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Escherichia coli MurZ
-
enzyme catalyzes the first committed step in the biosynthesis of bacterial cell wall peptidoglycan
-
-
-
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Enterobacter cloacae DSM 30054
-
enzyme catalyzes the first committed step in the biosynthesis of bacterial cell wall peptidoglycan
-
-
-
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Escherichia coli K-235
-
pathway for biosynthesis of UDP-N-acetylmuramic acid
-
-
-
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Enterobacter cloacae NRC 492
-
pathway for biosynthesis of UDP-N-acetylmuramic acid
-
-
-
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
phosphate + UDP-N-acetyl-3-(1-carboxyvinyl)-D-glucosamine
show the reaction diagram
Chlamydia trachomatis MurA
-
peptidoglycan formation is essential for progression through the developmental cycle as well as for cell division
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
not affected by K+, Na+, Mg2+, and Mn2+
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(E)-3-fluorophosphoenolpyruvate
-
pseudosubstrate, formation of a tetrahedral intermediate in the reaction pathway, investigation of chirality of the intermediate stereospecifically formed at the active site in D2O
(E)-3-fluorophosphoenolpyruvate
-
formation of 2 reaction intermediates: a covalent phosphofluorolactyl-enzyme adduct and a free phosphofluorolactyl-UDP-GlcNAc tetrahedral adduct; inactivation; kinetics
(S)-2-[2-(naphthalene-1-sulfonylamino)-5-(naphthalene-1-sulfonyloxy)-benzoylamino]-pentanedioic acid
-
competitive with UDP-N-acetylglucosamine
(S)-2-[2-(naphthalene-1-sulfonylamino)-5-(naphthalene-1-sulfonyloxy)-benzoylamino]-succinic acid
-
-
(Z)-3-fluorophosphoenolpyruvate
-
pseudosubstrate, formation of a tetrahedral intermediate in the reaction pathway, investigation of chirality of the intermediate stereospecifically formed at the active site in D2O
(Z)-3-fluorophosphoenolpyruvate
-
formation of 2 reaction intermediates: a covalent phosphofluorolactyl-enzyme adduct and a free phosphofluorolactyl-UDP-GlcNAc tetrahedral adduct; inactivation; kinetics
(Z)-3-fluorophosphoenolpyruvate
-
kinetics, mutant C115D; wild-type and mutant C115D, competitive against phosphoenolpyruvate
2-(4-methylpiperazin-1-yl)-3,4-dihydronaphthalen-1(2H)-one
-
-
2-oxo-1,3-benzoxathiol-5-yl (3-chlorophenyl)carbamate
-
-
2-oxo-1,3-benzoxathiol-5-yl methylcarbamate
-
-
2-oxo-1,3-benzoxathiol-5-yl pyridine-4-carboxylate
-
-
2-oxo-1,3-benzoxathiol-6-yl 4-nitrobenzenesulfonate
-
-
2-oxo-1,3-benzoxathiol-6-yl benzenesulfonate
-
-
2-oxo-1,3-benzoxathiol-6-yl methanesulfonate
-
-
2-oxo-1,3-benzoxathiol-6-yl sulfamate
-
-
2-[4-(2-hydroxyethyl)piperazin-1-yl]-3,4-dihydronaphthalen-1(2H)-one
-
-
2-[4-(2-hydroxyethyl)piperazin-1-yl]-6,7-dimethoxy-3,4-dihydronaphthalen-1(2H)-one
-
-
3-Bromopyruvate
-
irreversible, inhibitory effect is increased by UDP-GlcNAc
4,7-dichloro-5-hydroxy-1,3-benzoxathiol-2-one
-
-
5,5'-dithiobis(2-nitrobenzoic acid)
-
complete inhibition at 0.01 M; i.e. DTNB
5,7-dibromo-6-hydroxy-1,3-benzoxathiol-2-one
-
-
5-(prop-2-en-1-yloxy)-1,3-benzoxathiol-2-one
-
-
5-hydroxy-7-(3-methylphenyl)-1,3-benzoxathiol-2-one
-
-
5-hydroxy-7-(3-methylphenyl)-1,3-benzoxathiol-2-one
-
slight inhibition at 0.12 mM
5-hydroxy-7-(4-methoxyphenyl)-1,3-benzoxathiol-2-one
-
-
5-hydroxy-7-(4-methoxyphenyl)-1,3-benzoxathiol-2-one
-
slight inhibition at 0.12 mM
5-hydroxybenzo[d][1,3]oxathiol-2-one
-
-
-
5-hydroxynaphtho[1,2-d][1,3]oxathiol-2-one
-
-
5-hydroxynaphtho[2,1-d][1,3]oxathiol-2-one
-
-
5-methoxy-1,3-benzoxathiole
-
-
5-methoxy-1,3-benzoxathiole
-
slight inhibition at 0.12 mM
5-methoxybenzo[d][1,3]oxathiol-2-one
-
-
-
6,7-dimethoxy-2-[4-(2-phenylethyl)piperazin-1-yl]-3,4-dihydronaphthalen-1(2H)-one
-
-
7-(4-fluorophenyl)-5-hydroxy-1,3-benzoxathiol-2-one
-
-
7-(4-fluorophenyl)-5-hydroxy-1,3-benzoxathiol-2-one
-
slight inhibition at 0.12 mM
cnicin
-
sesquiterpene lactone. The enzyme catalyzes the formation of a covalent adduct between cnicin and substrate UDP-N-acetylglucosamine via an anti-Michael 1,3-addition of UDP-N-acetylglucosamine to an alpha,beta-unsaturated carbonyl function in cnicin thus forming a noncovalent suicide inhibitor
Co2+
-
metal ions do not enhance the activity of enzymes, activity is inhibited by 10 mM
Cu2+
-
metal ions do not enhance the activity of enzymes, activity is inhibited by 10 mM
ebselen
-
inhibitor covalently modifies the cysteine residue near the active site-loop of MurA, modification changes the open conformation of MurA to a more closed configuration, when compound is incubated for 30 min with dithiothreitol, its inhibitory activity against Haemophilus influenzae MurA is completely eliminated
Fe2+
-
metal ions do not enhance the activity of enzymes, activity is inhibited by 10 mM
-
fosfomycin
-
irreversible, active site SH-group is involved
fosfomycin
-
alkylates Cys115
fosfomycin
-
alkylates Cys115; competitive against phosphoenolpyruvate; inhibits the wild-type, mutant C155D is completely resistant; t1/2 for inactivation of the wild-type enzyme: 6 s
fosfomycin
-
binds covalently to Cys115
fosfomycin
-
binds covalently to Cys115
fosfomycin
-
binding study by isothermal titration calorimetry; binds covalently to Cys115
fosfomycin
-
resistant to fosfomycin inhibition due to exchange of cysteine for aspartate in the active site
fosfomycin
-
irreversible, alkylation of C115
fosfomycin
-
0.01 mM
fosfomycin
-
selectively inhibited by fosfomycin, which forms a covalent bond to the sulfhydryl group of the catalytically relevant Cys115 residue
fosfomycin
-
enolpyruvyl UDP-GlcNAc synthase is an antimicrobial target that is inhibited by the antibiotic fosfomycin
fosfomycin
-
despite low level expression during normal growth, murZ expression is strongly induced up to 6fold following exposure to inhibitors of peptidoglycan biosynthesis, minimum inhibitory concentration is 4 mg/ml; the naturally occurring antibiotic, which is an analogue of phosphoenolpyruvate, irreversibly inhibits the majority of MurA enzymes, fosfomycin minimum inhibitory concentration is 8 mg/ml, peptidoglycan content is reduced by approximately 25% following inactivation of murA
fosfomycin
-, B5F9P4
-
fosfomycin
H2DMJ3
-
fosfomycin
-
more than 90% inhibition at 0.2 mM
iodoacetamide
-
inhibition by alkylation of the active site Cys155, pH-dependent, no alkylation below pH 7.0, maximum alkylation at pH 9.0
N-ethylmaleimide
-
-
N-ethylmaleimide
-
complete inhibition at 0.2 M
p-chloromercuribenzoate
-
-
PEP 1354 peptide
-
competitive inhibitor
-
PGE-553828
-
competitive against UDP-GlcNAc; inhibition mechanism, kinetics
-
phosphoenol-2-ketovalerate
-
-
-
phosphonomycin
-
i.e. L-cis-2-epoxypropylphosphonic acid; inhibitor binding site is distinct from active site; irreversible inactivation, requires the presence of UDP-GlcNAc
-
phosphonomycin
-, P0A749
irreversible inactivation, requires the presence of UDP-GlcNAc
-
thimerosal
-
inhibitor covalently modifies the cysteine residue near the active site-loop of MurA, modification changes the open conformation of MurA to a more closed configuration, when compound is incubated for 30 min with dithiothreitol, its inhibitory activity against Haemophilus influenzae MurA is completely eliminated
thiram
-
inhibitor covalently modifies the cysteine residue near the active site-loop of MurA, modification changes the open conformation of MurA to a more closed configuration, when compound is incubated for 30 min with dithiothreitol, its inhibitory activity against Haemophilus influenzae MurA is completely eliminated
Trypsin
-
wild-type and mutant C115S, no protection via individually binding of substrates or inhibitor fosfomycin, but via binding of both, the 2 substrates and inhibitor fosfomycin
-
UDP-N-acetylmuramic acid
-
weak
UDP-N-acetylmuramic acid
-
-
UDP-N-acetylmuramic acid
-
competitive with phosphate
UDP-N-acetylmuramic acid
-
-
UDP-N-acetylmuramic acid-L-Ala
-
weak
UDP-N-acetylmuramic acid-L-Ala-D-Glu
-
weak
UDP-N-acetylmuramic acid-L-Ala-D-Glu
-
no inhibition
UDP-N-acetylmuramyl-L-Ala-D-Glu-meso-alpha,epsilon-diaminopimelic acid
-
inhibitor binding site is distinct from active site
UDP-N-acetylmuramyl-L-Ala-D-Glu-meso-alpha,epsilon-diaminopimelic acid
-
-
UDP-N-acetylmuramyl-L-Ala-D-Glu-meso-alpha,epsilon-diaminopimelic acid
-
above 1 mM
uridine diphospho-N-acetylmuramyl-L-Ala-D-gamma-Glu-meso-alpha,epsilon-diaminopimelic-acid-D-Ala-D-Ala
-
inhibitor binding site is distinct from active site
uridine diphospho-N-acetylmuramyl-L-Ala-D-gamma-Glu-meso-alpha,epsilon-diaminopimelic-acid-D-Ala-D-Ala
-
-
uridine diphospho-N-acetylmuramyl-L-Ala-D-gamma-Glu-meso-alpha,epsilon-diaminopimelic-acid-D-Ala-D-Ala
-
above 1 mM
Zn2+
-
metal ions do not enhance the activity of enzymes, activity is inhibited by 10 mM
MnCl2
-
metal ions do not enhance the activity of enzymes, activity is inhibited by 10 mM
additional information
-
no inhibition by UDP-galactose
-
additional information
-
no inhibition by pyruvate and fluoropyruvate
-
additional information
-
inhibitors derived from 5-sulfonoxy-anthranilic acid obstruct the transition from the open and unliganded to the closed UDP-N-acetylglucosamine liganded form
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
dithiothreitol
-
included in the assay reaction mixture
dithiothreitol
-
included in the assay reaction mixture
thiol groups
-
required for activity
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0004
-
phosphoenolpyruvate
-
wild-type enzyme
0.00045
-
phosphoenolpyruvate
-
0.125 mM Tris-HCl, pH 7.5
0.00045
-
phosphoenolpyruvate
-
pH and temperature not specified in the publication
0.00084
-
phosphoenolpyruvate
-
0.125 mM Tris-HCl, pH 7.5
0.004
-
phosphoenolpyruvate
-
pH and temperature not specified in the publication
0.0041
-
phosphoenolpyruvate
-
-
0.008
-
phosphoenolpyruvate
-
wild-type enzyme
0.0083
-
phosphoenolpyruvate
-
pH and temperature not specified in the publication
0.011
-
phosphoenolpyruvate
-
isoform MurA2
0.01148
-
phosphoenolpyruvate
-
50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6
0.01148
-
phosphoenolpyruvate
-
pH and temperature not specified in the publication
0.01157
-
phosphoenolpyruvate
-
50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6
0.022
-
phosphoenolpyruvate
-
mutant C115D, pH 6.0
0.024
-
phosphoenolpyruvate
-
wild type enzyme, at pH 7.8 and 25C
0.03
-
phosphoenolpyruvate
-
-
0.037
-
phosphoenolpyruvate
-
mutant C115D, pH 8.0
0.037
-
phosphoenolpyruvate
-
isoform MurA1
0.037
-
phosphoenolpyruvate
-
pH and temperature not specified in the publication
0.15
-
phosphoenolpyruvate
-
mutant enzyme C117D, at pH 6.0 and 25C
1
-
phosphoenolpyruvate
-, P0A749
-
0.0057
-
UDP-GlcNAc
-
-
0.015
-
UDP-GlcNAc
-
wild-type enzyme
0.016
-
UDP-GlcNAc
-
mutant C115D, pH 8.0
0.021
-
UDP-GlcNAc
-
mutant C115D, pH 6.0
0.08
-
UDP-GlcNAc
-
wild-type enzyme
0.12
-
UDP-GlcNAc
-
isoform MurA2
0.244
-
UDP-GlcNAc
-
isoform MurA1
0.46
-
UDP-GlcNAc
-
-
2.5
-
UDP-GlcNAc
-, P0A749
-
0.015
-
UDP-N-acetyl-D-glucosamine
-
pH and temperature not specified in the publication
0.0178
-
UDP-N-acetyl-D-glucosamine
-
0.125 mM Tris-HCl, pH 7.5
0.0178
-
UDP-N-acetyl-D-glucosamine
-
pH and temperature not specified in the publication
0.031
-
UDP-N-acetyl-D-glucosamine
-
wild type enzyme, at pH 7.8 and 25C
0.036
-
UDP-N-acetyl-D-glucosamine
-
0.125 mM Tris-HCl, pH 7.5
0.08
-
UDP-N-acetyl-D-glucosamine
-
pH and temperature not specified in the publication
0.1239
-
UDP-N-acetyl-D-glucosamine
-
50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6
0.1239
-
UDP-N-acetyl-D-glucosamine
-
pH and temperature not specified in the publication
0.16
-
UDP-N-acetyl-D-glucosamine
-
mutant enzyme C117D, at pH 6.0 and 25C
0.1686
-
UDP-N-acetyl-D-glucosamine
-
50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6
0.244
-
UDP-N-acetyl-D-glucosamine
-
pH and temperature not specified in the publication
additional information
-
additional information
-
Km values of mutant enzymes for the substrates
-
additional information
-
additional information
-
kinetics
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.76
-
fosfomycin
-
50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6
0.41
-
phosphoenolpyruvate
-
pH and temperature not specified in the publication
0.68
-
phosphoenolpyruvate
-
mutant enzyme C117D, at pH 6.0 and 25C
1.13
-
phosphoenolpyruvate
-
pH and temperature not specified in the publication
1.8
-
phosphoenolpyruvate
-
pH and temperature not specified in the publication
3
-
phosphoenolpyruvate
-
wild-type enzyme
3
-
phosphoenolpyruvate
-
pH and temperature not specified in the publication
3.5
-
phosphoenolpyruvate
-
wild type enzyme, at pH 7.8 and 25C
3.8
-
phosphoenolpyruvate
-
pH and temperature not specified in the publication
4.75
-
phosphoenolpyruvate
-, P0A749
cosubstrate UDP-N-acetyl-D-glucosamine; recombinant enzyme
0.41
-
UDP-GlcNAc
-
isoform MurA1
0.78
-
UDP-GlcNAc
-
isoform MurA2
3
-
UDP-GlcNAc
-
wild-type enzyme
8.9
-
UDP-GlcNAc
-
-
0.41
-
UDP-N-acetyl-D-glucosamine
-
pH and temperature not specified in the publication
0.68
-
UDP-N-acetyl-D-glucosamine
-
mutant enzyme C117D, at pH 6.0 and 25C
1.13
-
UDP-N-acetyl-D-glucosamine
-
pH and temperature not specified in the publication
1.8
-
UDP-N-acetyl-D-glucosamine
-
the calculated value for UDP is 40 times higher than that of ADP
1.8
-
UDP-N-acetyl-D-glucosamine
-
pH and temperature not specified in the publication
2.4
-
UDP-N-acetyl-D-glucosamine
-
the calculated value for UDP is 40times higher than that of ADP
3
-
UDP-N-acetyl-D-glucosamine
-
pH and temperature not specified in the publication
3.5
-
UDP-N-acetyl-D-glucosamine
-
wild type enzyme, at pH 7.8 and 25C
3.8
-
UDP-N-acetyl-D-glucosamine
-
pH and temperature not specified in the publication
4.75
-
UDP-N-acetyl-D-glucosamine
-, P0A749
cosubstrate phosphoenolpyruvate; recombinant enzyme
1.13
-
fosfomycin
-
50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6
additional information
-
additional information
-
kcat values of mutant enzymes for the substrates
-
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.000005
-
phosphoenolpyruvate
-
pH and temperature not specified in the publication
15572
0.000011
-
phosphoenolpyruvate
-
pH and temperature not specified in the publication
15572
0.00007
-
phosphoenolpyruvate
-
50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6
15572
0.0001
-
phosphoenolpyruvate
-
50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6
15572
0.00036
-
phosphoenolpyruvate
-
pH and temperature not specified in the publication
15572
0.004
-
phosphoenolpyruvate
-
pH and temperature not specified in the publication
15572
0.01
-
phosphoenolpyruvate
-
pH and temperature not specified in the publication
15572
0.0000017
-
UDP-N-acetyl-D-glucosamine
-
pH and temperature not specified in the publication
17661
0.000005
-
UDP-N-acetyl-D-glucosamine
-
50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6
17661
0.000009
-
UDP-N-acetyl-D-glucosamine
-
50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6
17661
0.000009
-
UDP-N-acetyl-D-glucosamine
-
pH and temperature not specified in the publication
17661
0.0000375
-
UDP-N-acetyl-D-glucosamine
-
pH and temperature not specified in the publication
17661
0.000101
-
UDP-N-acetyl-D-glucosamine
-
pH and temperature not specified in the publication
17661
0.00025
-
UDP-N-acetyl-D-glucosamine
-
pH and temperature not specified in the publication
17661
520000
-
additional information
-
MurA-catalyzed breakdown of its tetrahedral intermediate at pH 7.5, second-order rate constant
0
570000
-
additional information
-
MurA-catalyzed breakdown of its tetrahedral intermediate at pH 10.0
0
6000000
-
additional information
-
MurA-catalyzed breakdown of its tetrahedral intermediate at pH 5.0
0
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.04
-
(Z)-3-fluorophosphoenolpyruvate
-
at pH 8.0; wild-type enzyme
0.08
-
(Z)-3-fluorophosphoenolpyruvate
-
at pH 8.0; mutant C115D
0.1
-
(Z)-3-fluorophosphoenolpyruvate
-
at pH 6.0; mutant C115D
0.0086
-
fosfomycin
-
wild-type enzyme
1
-
fosfomycin
-
at pH 8.0; mutant C115D
0.038
-
PGE-553828
-
-
-
1.7
-
phosphoenol-2-ketovalerate
-
-
-
0.016
-
T6362
-
20C, pH 8.0
4.9
6.6
UDP-N-acetylmuramyl-L-Ala-D-Glu-meso-alpha,epsilon-diaminopimelic acid
-
-
0.8
-
uridine diphospho-N-acetylmuramyl-L-Ala-D-gamma-Glu-meso-alpha,epsilon-diaminopimelic-acid-D-Ala-D-Ala
-
-
2
-
fosfomycin
-
at pH 6.0; mutant C115D
additional information
-
additional information
-
-
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00853
-
2-(4-methylpiperazin-1-yl)-3,4-dihydronaphthalen-1(2H)-one
-
-
0.01204
-
2-(4-methylpiperazin-1-yl)-3,4-dihydronaphthalen-1(2H)-one
-
-
0.00286
-
2-oxo-1,3-benzoxathiol-5-yl (3-chlorophenyl)carbamate
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.00046
-
2-oxo-1,3-benzoxathiol-5-yl methylcarbamate
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.00058
-
2-oxo-1,3-benzoxathiol-5-yl pyridine-4-carboxylate
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.00515
-
2-oxo-1,3-benzoxathiol-6-yl 4-nitrobenzenesulfonate
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.01079
-
2-oxo-1,3-benzoxathiol-6-yl 4-nitrobenzenesulfonate
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.00196
-
2-oxo-1,3-benzoxathiol-6-yl benzenesulfonate
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.00668
-
2-oxo-1,3-benzoxathiol-6-yl benzenesulfonate
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.00076
-
2-oxo-1,3-benzoxathiol-6-yl methanesulfonate
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.00113
-
2-oxo-1,3-benzoxathiol-6-yl methanesulfonate
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.00025
-
2-oxo-1,3-benzoxathiol-6-yl sulfamate
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.00239
-
2-oxo-1,3-benzoxathiol-6-yl sulfamate
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.00243
-
2-oxo-1,3-benzoxathiol-6-yl sulfamate
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.01794
-
2-oxo-1,3-benzoxathiol-6-yl sulfamate
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.01252
-
2-[4-(2-hydroxyethyl)piperazin-1-yl]-3,4-dihydronaphthalen-1(2H)-one
-
-
0.02249
-
2-[4-(2-hydroxyethyl)piperazin-1-yl]-3,4-dihydronaphthalen-1(2H)-one
-
-
0.00313
-
2-[4-(2-hydroxyethyl)piperazin-1-yl]-6,7-dimethoxy-3,4-dihydronaphthalen-1(2H)-one
-
-
0.01735
-
2-[4-(2-hydroxyethyl)piperazin-1-yl]-6,7-dimethoxy-3,4-dihydronaphthalen-1(2H)-one
-
-
0.00028
-
4,7-dichloro-5-hydroxy-1,3-benzoxathiol-2-one
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.00109
-
4,7-dichloro-5-hydroxy-1,3-benzoxathiol-2-one
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.00095
-
5,7-dibromo-6-hydroxy-1,3-benzoxathiol-2-one
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.00349
-
5,7-dibromo-6-hydroxy-1,3-benzoxathiol-2-one
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.00801
-
5-(prop-2-en-1-yloxy)-1,3-benzoxathiol-2-one
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.00727
-
5-hydroxy-7-(3-methylphenyl)-1,3-benzoxathiol-2-one
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.00951
-
5-hydroxy-7-(4-methoxyphenyl)-1,3-benzoxathiol-2-one
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.00053
-
5-hydroxybenzo[d][1,3]oxathiol-2-one
-
in 50 mM Tris-HCl, pH 7.9, at 37C
-
0.02707
-
5-hydroxybenzo[d][1,3]oxathiol-2-one
-
in 50 mM Tris-HCl, pH 7.9, at 37C
-
0.0031
-
5-hydroxynaphtho[1,2-d][1,3]oxathiol-2-one
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.02431
-
5-hydroxynaphtho[1,2-d][1,3]oxathiol-2-one
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.00155
-
5-hydroxynaphtho[2,1-d][1,3]oxathiol-2-one
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.02609
-
5-hydroxynaphtho[2,1-d][1,3]oxathiol-2-one
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.01428
-
5-methoxy-1,3-benzoxathiole
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.00645
-
5-methoxybenzo[d][1,3]oxathiol-2-one
-
in 50 mM Tris-HCl, pH 7.9, at 37C
-
0.02479
-
5-methoxybenzo[d][1,3]oxathiol-2-one
-
in 50 mM Tris-HCl, pH 7.9, at 37C
-
0.02256
-
6,7-dimethoxy-2-[4-(2-phenylethyl)piperazin-1-yl]-3,4-dihydronaphthalen-1(2H)-one
-
-
0.029
-
6,7-dimethoxy-2-[4-(2-phenylethyl)piperazin-1-yl]-3,4-dihydronaphthalen-1(2H)-one
-
-
0.01854
-
7-(4-fluorophenyl)-5-hydroxy-1,3-benzoxathiol-2-one
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.0001
-
ebselen
-
50 mM Tris-HCl, pH 7.8, compound displays an anti-MurA activity that is above 90% at a concentration below 0.002 mM
0.00046
-
fosfomycin
-
-
0.00053
-
fosfomycin
-
enzyme is pre-incubated with the inhibitor in the presence of 1 mM UDP-N-acetyl-D-glucosamine, reaction is started by addition of phosphoenolpyruvate
0.0006
-
fosfomycin
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.00077
-
fosfomycin
-
enzyme is pre-incubated with the inhibitor in the presence of 1 mM UDP-N-acetyl-D-glucosamine, reaction is started by addition of phosphoenolpyruvate
0.00125
-
fosfomycin
-
in 50 mM Tris-HCl, pH 7.9, at 37C
0.00136
-
fosfomycin
-
-
0.00136
-
fosfomycin
-
50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6
0.00137
-
fosfomycin
-
50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6
0.0045
-
fosfomycin
-
enzyme shows 5-7fold shift in IC50 for the inhibitor upon pre-incubation with the substrate UDP-N-acetyl-D-glucosamine
0.0051
-
fosfomycin
-
enzyme shows 5-7fold shift in IC50 for the inhibitor upon pre-incubation with the substrate UDP-N-acetyl-D-glucosamine
0.0004
-
thimerosal
-
50 mM Tris-HCl, pH 7.8, compound displays an anti-MurA activity that is above 90% at a concentration below 0.002 mM
0.0007
-
thiram
-
50 mM Tris-HCl, pH 7.8, compound displays an anti-MurA activity that is above 90% at a concentration below 0.002 mM
0.04
-
fosfomycin
-
50 mM Tris-HCl, pH 7.8, compound displays an anti-MurA activity that is above 90% at a concentration below 0.002 mM
additional information
-
additional information
-
in wild-type background, IC50 of fosfomycin is 2,048 microg/ml. In a strain with antisense-based expression attenuation of the MurA1 gene encoding UDP-N-acetylglucosamine enolpyruvyl transferase, IC50 value is 126 microg/ml. Prsence of xylose further decreases the IC50 value to 18 microg/ml
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.1
0.12
-
partially purified enzyme
0.2
-
-
partially purified enzyme
0.27
-
-
purified enzyme
0.91
-
-
mutant enzyme C117D, at pH 6.0 and 25C
1.8
-
-
purified native enzyme
1.9
-
-
purified enzyme
4.7
-
-
wild type enzyme, at pH 7.8 and 25C
additional information
-
-
-
additional information
-
-
activity of K22 mutants compared to wild-type in forward and reverse reaction, coupled assay
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.4
-
-
assay at
7.5
-
-
assay at
8
-
-
assay at
additional information
-
-
determination of pKa value for Cys115: 8.3
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.5
10
-
recombinant enzyme, enzyme activity gradually decreases when the pH is below 5.5 or above 10.0
6
9
-
enzyme shows activity at wide range of pH
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
-
-
assay at
25
-
-
assay at
37
-
-
assay at
37
-
-
assay at
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
-
-, B6DVJ7
estimated
PDB
SCOP
CATH
ORGANISM
Aquifex aeolicus (strain VF5)
Aquifex aeolicus (strain VF5)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCDC 279-56)
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)
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e)
Streptococcus pneumoniae (strain Hungary19A-6)
Streptococcus pneumoniae serotype 2 (strain D39 / NCTC 7466)
Vibrio fischeri (strain MJ11)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
34000
-
-
gel filtration
37000
-
-
nondenaturing PAGE
44700
-
-, B6DVJ7
calculated from the 422 amino acids, confirmed by SDS-PAGE
44780
-
-
MW deduced from amino acid sequence
44780
-
-
electrospray ionization-mass spectrometry
44800
-
-, P0A749
MW deduced from amino acid sequence
45000
-
-
dynamic light scattering
89000
-
-
as fusion protein with maltose binding protein, determined by SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-, B5F9P4
x * 45640, calculated from amino acid sequence
?
Aliivibrio fischeri MJ11
-
x * 45640, calculated from amino acid sequence
-
monomer
-
1 * 41000, SDS-PAGE
monomer
-
42100, SDS-PAGE
monomer
-
1 * 46252, calculated from amino acid sequence, including a C-terminal tag
monomer
-
it appears to be a monomer in solution, even at high concentrations
monomer
Enterobacter cloacae DSM 30054
-
42100, SDS-PAGE
-
additional information
-
two-domain structure with the active site located between them, substrate binding structure
additional information
-
structure
additional information
Enterobacter cloacae MurA
-
structure
-
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
in complex with UDP-N-acetylglucosamine and fosfomycin, sitting drop vapor diffusion method, using 25% (w/v) PEG 3350, 0.1 M bis-Tris pH 6.5
-, B5F9P4
at 19C, from 10 mM MES, pH 6.4, 10% (w/v) polyethylene glycol 20000, in the presence of 5 mM UDP-N-acetyl-D-glucosamine and 5 mM phosphoenolpyruvate
-
crystallization of substrate-free enzyme, two-domain structure with an unusual fold, inside out alpha/beta barrel, which is built up from the 6fold repetititon of one folding unit, structure analysis
-
in complex with inhibitor T6361
-
in complex with substrates, hanging drop vapor diffusion method, using 0.1 M Bis-Tris (pH 5.5), 0.2 M NH4OAc, 25% (w/v) PEG 3350
-
mutant D305A, in presence of phosphoenolpyruvate and UDP-N-acetyl-D-glucosamine
-
X-ray structure analysis of ligated and unligated MurA
-
crystallization of the enzyme complexed with UDP-N-acetylglucosamine and fosfomycin, two-domain structure with the active site located between them, structure and substrate binding analysis
-
in complex with inhibitor cnicin and substrate UDP-N-acetylglucosamine, at 2.0 A resolution. The enzyme catalyzes the formation of a covalent adduct between cnicin and UDP-N-acetylglucosamine via an anti-Michael 1,3-addition of UDP-N-acetylglucosamine to an alpha,beta-unsaturated carbonyl function in cnicin thus forming a noncovalent suicide inhibitor
-
MurA is crystallized in the presence of sodium phosphite and UDP-N-acetylmuramic acid using the hanging drop vapor diffusion method, the MurA cocrystal structure with UDP-N-acetylmuramic acid and phosphite reveals a new staged MurA conformation in which the Arg397 side chain tracked phosphite out of the catalytic site
-
in complex with UDP-N-acetylglucosamine and fosfomycin, to 2.3 A resolution. The active-site loop can adopt one of the three major conformations: a fully open conformation, a half-open conformation, and a closed conformation. Fosfomycin can bind without inducing a large change in the half-open conformation of the binary complex with UDP-N-acetylglucosamine
-
in the apo-form, as well as in a complex with UDP-N-acetylglucosamine and fosfomycin using ammonium sulfate as the precipitant, hanging drop vapour diffusion method
-
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
no effect of 10% DMSO on the activity of enzyme
-
EDTA, DTT and dithioerythritol stabilize
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, loss of activity after 1 week
-
0C or -20C, 0.2 mg/ml DTT, 40% loss of activity after 2 weeks
-
4C, in 80% ammonium sulfate, loss of activity after 1 week
-
-15C, crude enzyme preparation, in presence of 4 mM DTT, loss of 84% activity within 2 weeks
-
-196C, 4 mM DTT, stable for up to 6 weeks, partially purified enzyme
-
-196C, slightly increased activity after storage of 2 weeks
-
-70C, 4 mM DTT, 22% loss of activity in 2 weeks, partially purified enzyme
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
by metal affinity chromatography with a nickel column
-, B6DVJ7
Ni-NTA agarose column chromatography and Superdex 75 gel filtration
-, B5F9P4
ammonium sulfate precipitation, phenyl-Sepharose column chromatography, Q-Sepharose column chromatography, Superdex 200 gel filtration, and Sephadex G-25 gel filtration
-
covalent adduct of enzyme and phosphoenolpyruvate
-
recombinant from Escherichia coli
-
recombinant wild-type and mutants from Escherichia coli
-
nickel affinity column chromatography
-
MurA purification is done by using self packed amylose resin column
-
native and recombinant from Escherichia coli
-, P0A749
on to a HiTrap QP-Sepharose HP ion exchange column
-
purified protein has significant amounts of UDP-N-acteylmuramic acid bound
-
recombinant from overexpresssing strain
-
Ni-NTA column chromatography and gel filtration
-
Ni-NTA resin chromatography, HiLoad XK 16 Superdex 200 prep-grade gel filtration, and Mono Q HR10/10 column chromatography
-
MurA purification is done by using self packed amylose resin column
-
by using affinity chromatography
-
recombinant, 2 isoforms from Escherichia coli
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expressed in Escherichia coli BL21 Star (DE3) cells
-, B5F9P4
overexpression in Escherichia coli with a 6-His tag
-, B6DVJ7
gene murA, DNA sequence analysis, expression in Escherichia coli under control of the arabinose-inducible, glucose-repressible ara promotor, functional complementation, necessary for viability, of a enzyme-deficient Escherichia coli murA null-mutant, impartment of fosfomycin resistance to the Escherichia coli cell
-
DNA and amino acid sequence determination, functional overexpression in Escherichia coli strain JM105
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Escherichia coli STBL2-DE3 cells
-
expression of wild-type and mutants in Escherichia coli
-
expressed in an Enterococcus faecalis mutant lacking IreK (formerly PrkC), a key kinase required for cephalosporin resistance, and in Escherichia coli BL21(DE3) cells
-
cloning and expression of MurA using pMAL expression system in frame with the fusion maltose binding protein in Escherichia coli BL21
-
DNA and amino acid sequence determination and analysis, chromosome mapping at 69.3 min, overexpression in Escherichia coli strain JLM 16
-, P0A749
expression from plasmid in Escherichia coli deletion mutant, functional complementation
P0A749
overexpression in Escherichia coli
-
overexpression of wild type MurA
-
coding region of Haemophilus influenzae MurA is cloned into the NdeI and XhoI sites of pET21a to generate an expression vector for MurA, the expression vector is transformed into Escherichia coli Rosetta2 (DE3), and the recombinant MurA is expressed
-
expressed in Escherichia coli
-
expression in Escherichia coli
-
cloning and expression of MurA using pMAL expression system in frame with the fusion maltose binding protein in Escherichia coli BL21
-
the murA gene is cloned and overexpressed in Escherichia coli with a C-terminal 6-His tag; the murZ gene is cloned and overexpressed in Escherichia coli with a C-terminal 6-His tag
-
genes murA1 and murA2, DNA and amino acid sequence determination, overexpression of both isoforms in Escherichia coli BL21(DE3)
-
expressed in Escherichia coli DH5alpha cells
H2DMJ3
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C115D
-
the mutant enzyme lacks the ability to react with phosphoenolpyruvate covalently
C115S
-
mutant enzyme is capable of catalyzing the wild type enzyme reaction but is unable to release the products (single turnover), activity is not affected by fosfomycin
C251S
-
site-directed mutagenesis, Cys251 is not involved in the catalysis, unaltered biochemical properties
C354S
-
site-directed mutagenesis, Cys354 is not involved in the catalysis, unaltered biochemical properties
C381S
-
site-directed mutagenesis, Cys381 is not involved in the catalysis, unaltered biochemical properties
D305A
-
site-directed mutagenesis, weaker binding of UDP-GlcNAc, no activity, fosfomycin is not covalently attached to Cys115
D305A
-
crystallization data
D305C
-
site-directed mutagenesis, weaker binding of UDP-GlcNAc, no activity
D305E
-
site-directed mutagenesis, weaker binding of UDP-GlcNAc, 0.1% activity compared to the wild-type
D305H
-
site-directed mutagenesis, weaker binding of UDP-GlcNAc, no activity, fosfomycin is not covalently attached to Cys115
K22E
-
site-directed mutagenesis, exchange of conserved Lys residue located near the active site and involved in substrate binding leading to conformational changes, shows less than 0.5% activity compared to the wild-type, altered UDP-GlcNAc binding, highly reduced formation of covalent adduct between active site Cys115 and phosphoenolpyruvate or inhibitor fosfomycin
K22E
-
0.05% of wild-type activity, no formation of covalent adduct with fosfomycin
K22R
-
site-directed mutagenesis, exchange of conserved Lys residue located near the active site and involved in substrate binding leading to conformational changes, shows less than 0.5% activity compared to the wild-type, slightly reduced formation of covalent adduct between active site Cys115 and phosphoenolpyruvate or inhibitor fosfomycin
K22R
-
0.3% of wild-type activity
K22V
-
site-directed mutagenesis, exchange of conserved Lys residue located near the active site and involved in substrate binding leading to conformational changes, shows less than 0.5% activity compared to the wild-type, reduced formation of covalent adduct between active site Cys115 and phosphoenolpyruvate or inhibitor fosfomycin
K22V
-
0.03% of wild-type activity, similar to wild-type in binding of fosfomycin, presence of UDP-N-acetylglucosamine required
K22V/R120K
-
no residual activity, heat capacity changes are markedly redcued
K22V/R120V
-
no residual activity
N23A
-
site-directed mutagenesis, reduced activity, 20fold higher apparent dissociation constant for fosfomycin compared to wild-type
N23S
-
site-directed mutagenesis, reduced activity, 200fold higher apparent dissociation constant for fosfomycin compared to wild-type
R120K
-
less than 0.05% of wild-type activity, heat capacity changes are markedly redcued
C115S
Enterobacter cloacae MurA
-
-
-
C251S
Enterobacter cloacae MurA
-
site-directed mutagenesis, Cys251 is not involved in the catalysis, unaltered biochemical properties
-
C354S
Enterobacter cloacae MurA
-
site-directed mutagenesis, Cys354 is not involved in the catalysis, unaltered biochemical properties
-
C381S
Enterobacter cloacae MurA
-
site-directed mutagenesis, Cys381 is not involved in the catalysis, unaltered biochemical properties
-
D305A
Enterobacter cloacae MurA
-
site-directed mutagenesis, weaker binding of UDP-GlcNAc, no activity, fosfomycin is not covalently attached to Cys115
-
D305C
Enterobacter cloacae MurA
-
site-directed mutagenesis, weaker binding of UDP-GlcNAc, no activity
-
D305E
Enterobacter cloacae MurA
-
site-directed mutagenesis, weaker binding of UDP-GlcNAc, 0.1% activity compared to the wild-type
-
N23A
Enterobacter cloacae MurA
-
site-directed mutagenesis, reduced activity, 20fold higher apparent dissociation constant for fosfomycin compared to wild-type
-
N23S
Enterobacter cloacae MurA
-
site-directed mutagenesis, reduced activity, 200fold higher apparent dissociation constant for fosfomycin compared to wild-type
-
C120S
-
catalytically inactive
C115A
-
site-directed mutagenesis, overexpression in Escherichia coli, no activity
C115D
-
site-directed mutagenesis, overexpression in Escherichia coli, gains fosfomycin resistance, forms only the phospholactyl-enzyme intermediate adduct, but no UDP-GlcNAc-phosphoenolpyruvate, higher kcat than the wild-type at pH 7.0, enhanced pH-dependency of the reaction
C115D
-
mutant protein is functional and resistant to fosfomycin and inhibitors 2-[4-(2-hydroxyethyl)piperazin-1-yl]-6,7-dimethoxy-3,4-dihydronaphthalen-1(2H)-one and2-(4-methylpiperazin-1-yl)-3,4-dihydronaphthalen-1(2H)-one
C115E
-
site-directed mutagenesis, overexpression in Escherichia coli, gains fosfomycin resistance, enhanced pH-dependency of the reaction, low activity
C115N
-
site-directed mutagenesis, overexpression in Escherichia coli, deamination of Asn115 to Asp115
C115A
Escherichia coli MurA
-
site-directed mutagenesis, overexpression in Escherichia coli, no activity
-
C115D
Escherichia coli MurA
-
site-directed mutagenesis, overexpression in Escherichia coli, gains fosfomycin resistance, forms only the phospholactyl-enzyme intermediate adduct, but no UDP-GlcNAc-phosphoenolpyruvate, higher kcat than the wild-type at pH 7.0, enhanced pH-dependency of the reaction
-
C115E
Escherichia coli MurA
-
site-directed mutagenesis, overexpression in Escherichia coli, gains fosfomycin resistance, enhanced pH-dependency of the reaction, low activity
-
C115N
Escherichia coli MurA
-
site-directed mutagenesis, overexpression in Escherichia coli, deamination of Asn115 to Asp115
-
C115S
Escherichia coli MurA
-
site-directed mutagenesis, overexpression in Escherichia coli, no activity
-
C117D
-
the mutation shifts ithe optimum pH from 7.8 to 6.0. The mutant is not inhibited by 1 mM fosfomycin
D120C
H2DMJ3
the mutant shows resistance against fosfomycin
additional information
-
antisense-based modulation of murA1 gene expression, which encodes UDP-N-acetylglucosamine enolpyruvyl transferase, hypersensitizes cells to the MurA-specific antibiotic fosfomycin despite the normally high resistance of Bacillus anthracis to this drug
C115S
-
site-directed mutagenesis, overexpression in Escherichia coli, no activity
additional information
P0A749
construction of a murA(Z) deletion mutant strain without catalytic activity, cells grow only when complemented by the enzyme expressed from a plasmid
C115D
-
mutant protein is functional and resistant to fosfomycin and inhibitors 2-[4-(2-hydroxyethyl)piperazin-1-yl]-6,7-dimethoxy-3,4-dihydronaphthalen-1(2H)-one and2-(4-methylpiperazin-1-yl)-3,4-dihydronaphthalen-1(2H)-one
additional information
-
individually inactivation of the 2 isoforms by allelic replacement shows, that the 2 forms can substitute for each other, a double deletion mutant is not viable
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
drug development
-, B6DVJ7
MurA will be a useful target to identify potential inhibitors of fosfomycin resistance in pharmacological studies
medicine
-
target for development of antibacterial agents
medicine
Chlamydia trachomatis MurA
-
target for development of antibacterial agents
-
medicine
P33038
enzyme is a target for the antibiotic fosfomycin
drug development
-
enzyme is an ideal target for the discovery of novel antibiotics against gram-negative pathogens as they have only one copy of murA gene in its genome
medicine
-
enzyme is a target for the antibiotic fosfomycin
medicine
-
target for development of antibacterial agents
medicine
Escherichia coli MurA
-
target for development of antibacterial agents
-
drug development
-
enzyme is an ideal target for the discovery of novel antibiotics against gram-negative pathogens as they have only one copy of murA gene in its genome
drug development
-
cell-wall synthesis is an important target for antibacterial agents, and MurA is one of the few enzymes involved in the cytoplasmic stage of peptidoglycan biosynthesis which is specifically inhibited by an existing antimicrobial agent