T00109
type: Enzyme
rlcp: p1181
rlcp: p1190
cath: Rossmann fold
cath: UDP-N-acetylmuramoyl-L-alanine
cath: Protein-Tyrosine Phosphatase; Chain A
ec: https://purl.uniprot.org/enzyme/6.3.2.9
csa: 1uag
macie: M0317
uniprot: P14900
kegg enzyme: UDP-N-acetylmuramoyl-L-alanine---D-glutamate ligase
kegg enzyme: MurD synthetase
kegg enzyme: UDP-N-acetylmuramoyl-L-alanyl-D-glutamate synthetase
kegg enzyme: uridine diphospho-N-acetylmuramoylalanyl-D-glutamate synthetase
kegg enzyme: D-glutamate-adding enzyme
kegg enzyme: D-glutamate ligase
kegg enzyme: UDP-Mur-NAC-L-Ala:D-Glu ligase
kegg enzyme: UDP-N-acetylmuramoyl-L-alanine:glutamate ligase (ADP-forming)
kegg enzyme: UDP-N-acetylmuramoylalanine---D-glutamate ligase
kegg pathway: D-Glutamine and D-glutamate metabolism
kegg pathway: Peptidoglycan biosynthesis
kegg cofactor: Magnesium
kegg substrate: ATP
kegg substrate: UDP-N-acetylmuramoyl-L-alanine
kegg substrate: Glutamate
kegg product: ADP
kegg product: Orthophosphate
kegg product: UDP-N-acetylmuramoyl-L-alanyl-D-glutamate
pdb: 1e0dA01
pdb: 1eehA01
pdb: 1uagA01
pdb: 2uagA01
pdb: 3uagA01
pdb: 4uagA01
pdb: 1e0dA02
pdb: 1eehA03
pdb: 1uagA02
pdb: 2uagA02
pdb: 3uagA02
pdb: 4uagA02
pdb: 1e0dA03
pdb: 1eehA02
pdb: 1uagA03
pdb: 2uagA03
pdb: 3uagA03
pdb: 4uagA03
pdb bound state: Unbound
  compound: ATP
  pdb: 1e0dA01
pdb bound state: Unbound
  compound: ATP
  pdb: 1eehA01
pdb bound state: Unbound
  compound: ATP
  pdb: 1uagA01
pdb bound state: Unbound
  compound: ATP
  pdb: 2uagA01
pdb bound state: Unbound
  compound: ATP
  pdb: 3uagA01
pdb bound state: Unbound
  compound: ATP
  pdb: 4uagA01
pdb bound state: Unbound
  compound: ATP
  pdb: 1e0dA02
pdb bound state: Unbound
  compound: ATP
  pdb: 1eehA03
pdb bound state: Unbound
  compound: ATP
  pdb: 1uagA02
pdb bound state: Unbound
  compound: ATP
  pdb: 2uagA02
pdb bound state: Unbound
  compound: ATP
  pdb: 3uagA02
pdb bound state: Unbound
  compound: ATP
  pdb: 4uagA02
pdb bound state: Unbound
  compound: ATP
  pdb: 1e0dA03
pdb bound state: Unbound
  compound: ATP
  pdb: 1eehA02
pdb bound state: Unbound
  compound: ATP
  pdb: 1uagA03
pdb bound state: Unbound
  compound: ATP
  pdb: 2uagA03
pdb bound state: Unbound
  compound: ATP
  pdb: 3uagA03
pdb bound state: Unbound
  compound: ATP
  pdb: 4uagA03
pdb bound state: Unbound
  compound: UDP-N-acetylmuramoyl-L-alanine
  pdb: 1e0dA01
pdb bound state: Unbound
  compound: UDP-N-acetylmuramoyl-L-alanine
  pdb: 1eehA01
pdb bound state: Unbound
  compound: UDP-N-acetylmuramoyl-L-alanine
  pdb: 1uagA01
pdb bound state: Unbound
  compound: UDP-N-acetylmuramoyl-L-alanine
  pdb: 2uagA01
pdb bound state: Unbound
  compound: UDP-N-acetylmuramoyl-L-alanine
  pdb: 3uagA01
pdb bound state: Unbound
  compound: UDP-N-acetylmuramoyl-L-alanine
  pdb: 4uagA01
active site residues resources: "Open" structures of MurD: domain movements and structural similarities with folylpolyglutamate synthetase.
active site residues resources: 2uag
references: Crystal structure of UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase from Escherichia coli.
references: Large-scale preparation, purification, and crystallization of UDP-N-acetylmuramoyl-L-alanine: D-glutamate ligase from Escherichia coli.
references: Determination of the MurD mechanism through crystallographic analysis of enzyme complexes.
references: "Open" structures of MurD: domain movements and structural similarities with folylpolyglutamate synthetase.
references: Structural and functional similarities in the ADP-forming amide bond ligase superfamily: implications for a substrate-induced conformational change in folylpolyglutamate synthetase.
references: Crystal structure of Escherichia coli UDPMurNAc-tripeptide d-alanyl-d-alanine-adding enzyme (MurF) at 2.3 A resolution.
references: Crystal structure of UDP-N-acetylmuramoyl-L-alanyl-D-glutamate: meso-diaminopimelate ligase from Escherichia coli.
comment: This enzyme catalyzes two successive transfer reactions, according to the literature [1] & [3]. Firstly, it transfers phosphate group from ATP to the carboxyl group of the second substrate, UDP-MurNAc (UMA), forming an acyl-phosphate intermediate. Secondly, it transfers acyl group (UMA) to the amine group of the other substrate, D-glutamate, releasing the inorganic phosphate. The first reaction (phosphate transfer) occurs as follows (see [3]): (1) The acceptor group, carboxyl oxygen atom of UMA, makes a nucleophilic attack on the transferred group, the phosphorus atom of the gamma-phosphate group of ATP. The reaction proceeds through an SN2-mechanism. (2) Lys115 and Mg2+ at site-2 stabilize the transition-state by neutralizing the transferred and leaving group, which are the beta- and gamma-phosphate groups of ATP. (3) Mg2+ at site-1 activates the acceptor group, the carboxyl group of UMA, and stabilizes the transferred group, the gamma-phosphate group of ATP. The second reaction (acyl transfer) occurs as follows (see [3]): (1') The first base, probably the gamma-phosphate group of the substrate, may abstract the proton from the second acceptor group, the amine group of D-Glu. (2') After the third substrate, D-Glu, was bound to the active site, the acceptor group, the amine group of D-Glu, would make a nucleophilic attack on the second transferred group, the carbonyl carbon of phosphorylated-UMA, forming the tetrahedral intermediate. (3') The second base, probably His183, may abstract the proton from the amine of the tetrahedral intermediate, facilitating the transformation of the intermediate into the final product and the release of the phosphate.

Rossmann fold
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.40.50.720

UDP-N-acetylmuramoyl-L-alanine
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.40.1190.10
catalytic domain: index.html

Protein-Tyrosine Phosphatase; Chain A
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.90.190.20

D-Glutamine and D-glutamate metabolism
type: KeggPathway
references: KEGG:MAP00471

Peptidoglycan biosynthesis
type: KeggPathway
references: KEGG:MAP00550

Magnesium
type: KeggCofactor
references: KEGG:C00305
compound type: divalent metal (Ca2+, Mg2+)
references: CHEBI:18420
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

ATP
type: KeggSubstrate
references: KEGG:C00002
compound type: amine group
compound type: nucleotide
references: CHEBI:15422
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

UDP-N-acetylmuramoyl-L-alanine
type: KeggSubstrate
references: KEGG:C01212
compound type: amino acids
compound type: amide group
compound type: carbohydrate
compound type: nucleotide
references: CHEBI:84726
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Glutamate
type: KeggSubstrate
references: KEGG:C00302
compound type: amino acids
compound type: carboxyl group
references: CHEBI:18237
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

ADP
type: KeggProduct
references: KEGG:C00008
compound type: amine group
compound type: nucleotide
references: CHEBI:16761
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Orthophosphate
type: KeggProduct
references: KEGG:C00009
compound type: phosphate group/phosphate ion
references: CHEBI:26078
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

UDP-N-acetylmuramoyl-L-alanyl-D-glutamate
type: KeggProduct
references: KEGG:C00692
compound type: amino acids
compound type: amide group
compound type: carbohydrate
compound type: carboxyl group
compound type: nucleotide
compound type: peptide/protein
references: CHEBI:46143
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

1e0dA02
type: Pdb
references: 1e0d
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1e0d
catalytic residue: LYS 115;ASN 138;
cofactor binding residue: SER 116;GLU 157(Magnesium-2);
comment: invisible H183

1eehA03
type: Pdb
references: 1eeh
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1eeh
catalytic residue: LYS 115;ASN 138;HIS 183
cofactor binding residue: SER 116;GLU 157(Magnesium-2);HIS 183(Magnesium-1)

1uagA02
type: Pdb
references: 1uag
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1uag
catalytic residue: LYS 115;ASN 138;HIS 183
cofactor binding residue: SER 116;GLU 157(Magnesium-2);HIS 183(Magnesium-1)
modified residue: KCX 198(carbanated Lys)

2uagA02
type: Pdb
references: 2uag
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:2uag
catalytic residue: LYS 115;ASN 138;HIS 183
cofactor binding residue: SER 116;GLU 157(Magnesium-2);HIS 183(Magnesium-1)
modified residue: KCX 198(carbamated Lys)

3uagA02
type: Pdb
references: 3uag
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3uag
catalytic residue: LYS 115;ASN 138;HIS 183
cofactor binding residue: SER 116;GLU 157(Magnesium-2);HIS 183(Magnesium-1)
modified residue: KCX 198(carbamated Lys)

4uagA02
type: Pdb
references: 4uag
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:4uag
catalytic residue: LYS 115;ASN 138;HIS 183
cofactor binding residue: SER 116;GLU 157(Magnesium-2);HIS 183(Magnesium-1)
modified residue: KCX 198(carbamated Lys)

Crystal structure of UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase from Escherichia coli.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
medline id: 97361823
references: http://www.ncbi.nlm.nih.gov/pubmed/9218784
journal: EMBO J
volume: 16
pages: 3416-25
published year: 1997
authors:
  item: Bertrand JA
  item: Auger G
  item: Fanchon E
  item: Martin L
  item: Blanot D
  item: van Heijenoort J
  item: Dideberg O
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P14900

Large-scale preparation, purification, and crystallization of UDP-N-acetylmuramoyl-L-alanine: D-glutamate ligase from Escherichia coli.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9631510
journal: Protein Expr Purif
volume: 13
pages: 23-9
published year: 1998
authors:
  item: Auger G
  item: Martin L
  item: Bertrand J
  item: Ferrari P
  item: Fanchon E
  item: Vaganay S
  item: Petillot Y
  item: van Heijenoort J
  item: Blanot D
  item: Dideberg O

Determination of the MurD mechanism through crystallographic analysis of enzyme complexes.
type: BibliographicResource
comment: X-ray crystallography
references: http://www.ncbi.nlm.nih.gov/pubmed/10356330
journal: J Mol Biol
volume: 289
pages: 579-90
published year: 1999
authors:
  item: Bertrand JA
  item: Auger G
  item: Martin L
  item: Fanchon E
  item: Blanot D
  item: Le Beller D
  item: van Heijenoort J
  item: Dideberg O
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

"Open" structures of MurD: domain movements and structural similarities with folylpolyglutamate synthetase.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
medline id: 20425115
references: http://www.ncbi.nlm.nih.gov/pubmed/10966819
journal: J Mol Biol
volume: 301
pages: 1257-66
published year: 2000
authors:
  item: Bertrand JA
  item: Fanchon E
  item: Martin L
  item: Chantalat L
  item: Auger G
  item: Blanot D
  item: van Heijenoort J
  item: Dideberg O
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P14900

Structural and functional similarities in the ADP-forming amide bond ligase superfamily: implications for a substrate-induced conformational change in folylpolyglutamate synthetase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10970743
journal: J Mol Biol
volume: 302
pages: 427-40
published year: 2000
authors:
  item: Sheng Y
  item: Sun X
  item: Shen Y
  item: Bognar AL
  item: Baker EN
  item: Smith CA

Crystal structure of Escherichia coli UDPMurNAc-tripeptide d-alanyl-d-alanine-adding enzyme (MurF) at 2.3 A resolution.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11090285
journal: J Mol Biol
volume: 304
pages: 435-45
published year: 2000
authors:
  item: Yan Y
  item: Munshi S
  item: Leiting B
  item: Anderson MS
  item: Chrzas J
  item: Chen Z

Crystal structure of UDP-N-acetylmuramoyl-L-alanyl-D-glutamate: meso-diaminopimelate ligase from Escherichia coli.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11124264
journal: J Biol Chem
volume: 276
pages: 10999-1006
published year: 2001
authors:
  item: Gordon E
  item: Flouret B
  item: Chantalat L
  item: van Heijenoort J
  item: Mengin-Lecreulx D
  item: Dideberg O

Analogue
compound: Magnesium
pdb: 3uagA02
ligand het code: _MN

Analogue
compound: Orthophosphate
pdb: 1uagA02
ligand het code: SO4

Analogue
compound: Orthophosphate
pdb: 4uagA02
ligand het code: SO4

ReferenceForCatalyticMechanism
reference index: 1
reference section: Fig.6, p.3422

ReferenceForCatalyticMechanism
reference index: 3
reference section: Fig.8, p.587-588