D00513
type: Enzyme
rlcp: p8010
rlcp: p131
rlcp: p1
cath: UDP-galactose 4-epimerase; domain 1
cath: Rossmann fold
ec: https://purl.uniprot.org/enzyme/4.2.1.47
uniprot: P93031
kegg enzyme: GDP-mannose 4,6-dehydratase
kegg enzyme: guanosine 5'-diphosphate-D-mannose oxidoreductase
kegg enzyme: guanosine diphosphomannose oxidoreductase
kegg enzyme: guanosine diphosphomannose 4,6-dehydratase
kegg enzyme: GDP-D-mannose dehydratase
kegg enzyme: GDP-D-mannose 4,6-dehydratase
kegg enzyme: Gmd
kegg enzyme: GDP-mannose 4,6-hydro-lyase
kegg pathway: Fructose and mannose metabolism
kegg cofactor: NADP+
kegg substrate: GDP-mannose
kegg product: GDP-4-dehydro-6-deoxy-D-mannose
kegg product: H2O
kegg intermediate: GDP-4-dehydro-mannose
kegg intermediate: GDP-4,5-ene-mannose
kegg intermediate: GDP-6-deoxy-4-dehydro-5,6-ene-mannose
pdb: 1n7gA01
pdb: 1n7gB01
pdb: 1n7gC01
pdb: 1n7gD01
pdb: 1n7hA01
pdb: 1n7hB01
pdb: 1n7gA02
pdb: 1n7gB02
pdb: 1n7gC02
pdb: 1n7gD02
pdb: 1n7hA02
pdb: 1n7hB02
pdb bound state: Unbound
  compound: GDP-mannose
  pdb: 1n7gA01
pdb bound state: Unbound
  compound: GDP-mannose
  pdb: 1n7gB01
pdb bound state: Unbound
  compound: GDP-mannose
  pdb: 1n7gC01
pdb bound state: Unbound
  compound: GDP-mannose
  pdb: 1n7gD01
pdb bound state: Analogue
  compound: GDP-mannose
  pdb: 1n7hA01
  ligand het code: GDP
pdb bound state: Analogue
  compound: GDP-mannose
  pdb: 1n7hB01
  ligand het code: GDP
pdb bound state: Unbound
  compound: GDP-mannose
  pdb: 1n7gA02
pdb bound state: Unbound
  compound: GDP-mannose
  pdb: 1n7gB02
pdb bound state: Unbound
  compound: GDP-mannose
  pdb: 1n7gC02
pdb bound state: Unbound
  compound: GDP-mannose
  pdb: 1n7gD02
pdb bound state: Unbound
  compound: GDP-mannose
  pdb: 1n7hA02
pdb bound state: Unbound
  compound: GDP-mannose
  pdb: 1n7hB02
pdb bound state: Unbound
  compound: NADP+
  pdb: 1n7gA01
pdb bound state: Unbound
  compound: NADP+
  pdb: 1n7gB01
pdb bound state: Unbound
  compound: NADP+
  pdb: 1n7gC01
pdb bound state: Unbound
  compound: NADP+
  pdb: 1n7gD01
pdb bound state: Unbound
  compound: NADP+
  pdb: 1n7hA01
pdb bound state: Unbound
  compound: NADP+
  pdb: 1n7hB01
pdb bound state: Analogue
  compound: GDP-4-dehydro-6-deoxy-D-mannose
  pdb: 1n7gA01
  ligand het code: GDR
pdb bound state: Analogue
  compound: GDP-4-dehydro-6-deoxy-D-mannose
  pdb: 1n7gB01
  ligand het code: GDR
pdb bound state: Analogue
  compound: GDP-4-dehydro-6-deoxy-D-mannose
  pdb: 1n7gC01
  ligand het code: GDR
pdb bound state: Unbound
  compound: GDP-4-dehydro-6-deoxy-D-mannose
  pdb: 1n7gD01
pdb bound state: Unbound
  compound: GDP-4-dehydro-6-deoxy-D-mannose
  pdb: 1n7hA01
pdb bound state: Unbound
  compound: GDP-4-dehydro-6-deoxy-D-mannose
  pdb: 1n7hB01
pdb bound state: Unbound
  compound: GDP-4-dehydro-6-deoxy-D-mannose
  pdb: 1n7gA02
pdb bound state: Unbound
  compound: GDP-4-dehydro-6-deoxy-D-mannose
  pdb: 1n7gB02
pdb bound state: Unbound
  compound: GDP-4-dehydro-6-deoxy-D-mannose
  pdb: 1n7gC02
pdb bound state: Unbound
  compound: GDP-4-dehydro-6-deoxy-D-mannose
  pdb: 1n7gD02
pdb bound state: Unbound
  compound: GDP-4-dehydro-6-deoxy-D-mannose
  pdb: 1n7hA02
pdb bound state: Unbound
  compound: GDP-4-dehydro-6-deoxy-D-mannose
  pdb: 1n7hB02
pdb bound state: Unbound
  compound: GDP-4-dehydro-mannose
  pdb: 1n7gA01
pdb bound state: Unbound
  compound: GDP-4-dehydro-mannose
  pdb: 1n7gB01
pdb bound state: Unbound
  compound: GDP-4-dehydro-mannose
  pdb: 1n7gC01
pdb bound state: Unbound
  compound: GDP-4-dehydro-mannose
  pdb: 1n7gD01
active site residues resources: Identification and characterization of GDP-d-mannose 4,6-dehydratase and GDP-l-fucose snthetase in a GDP-l-fucose biosynthetic gene cluster from Helicobacter pylori.
active site residues resources: Crystal structure of a tetrameric GDP-D-mannose 4,6-dehydratase from a bacterial GDP-D-rhamnose biosynthetic pathway.
active site residues resources: Chemical insights from structural studies of enzymes.
references: Structural and kinetic analysis of Escherichia coli GDP-mannose 4,6 dehydratase provides insights into the enzyme's catalytic mechanism and regulation by GDP-fucose.
references: Identification and characterization of GDP-d-mannose 4,6-dehydratase and GDP-l-fucose snthetase in a GDP-l-fucose biosynthetic gene cluster from Helicobacter pylori.
references: Identification of two GDP-6-deoxy-D-lyxo-4-hexulose reductases synthesizing GDP-D-rhamnose in Aneurinibacillus thermoaerophilus L420-91T.
references: Structure of the MUR1 GDP-mannose 4,6-dehydratase from Arabidopsis thaliana: implications for ligand binding and specificity.
references: Crystal structure of a tetrameric GDP-D-mannose 4,6-dehydratase from a bacterial GDP-D-rhamnose biosynthetic pathway.
references: Chemical insights from structural studies of enzymes.
comment: This enzyme belongs to the Short-chain dehydrogenases/reductases (SDR). Although a catalytic residue is different, this enzyme is homologous to the counterpart enzyme from bacteria and human (D00543 in EzCatDB). This enzyme catalyzes reactions similar to those by its homologous enzyme, dTDP-D-glucose-4,6-dehydratase (EC 4.2.1.46, D00262 in EzCatDB) (see [5] and [6]). The difference from the homologous enzyme is that this enzyme has only one acidic residue as a general acid/base, whearas the homologue uses two acidic residues. According to the literature [4], [5] and [6], this enzyme catalyzes at least three reactions: oxidation of GDP-mannose (hydride transfer from GDP-mannose to nicotinamide), dehydration (elimination of a hydroxyl group from C6), and rereduction of C5-C6 double bond to methyl group (hydride transfer from nicotinamide to the intermediate). Taken together, this enzyme catalyzes the following reactions: (A) Hydride transfer from C4 atom of substrate to NADP, forming a 4-keto intermediate (I00088): (A0) Lys189 (of 1n7g) modulates the activity (or pKa) of Tyr185 via 2'-hydroxyl group of NADP, along with the N1 atom of the nicotinamide group in NADP, whereas Ser162 modulates the pKa of 4-hydroxyl oxygen of the substrate. (A1) Tyr185 acts as a general base to deprotonate the 4-hydroxyl oxygen of the substrate. Meanwhile, the hydride transfer occurs from the C4-carbon of the substrate to the C4 atom of the nicotinamide, forming 4-keto intermediate. (B) Isomerization from the 4-keto intermediato to form an enol/enolate intermediate (I00089): (B0) Arg253 might modulate the pKa of Glu164 as a general base. Moreover, the 4-keto carbonyl group may increase the acidity of the C5 atom. (B1) Glu164 acts as a general base to deprotonate the C5 atom, leading to formation of enol/enolate intermediate. (C) Elimination of hydroxyl group from C6 of the enol/enolate intermediate, forming 4-keto-5,6-mannosen intermediate (I00090): (C0) GDP-phosphoryl groups in the interm…

UDP-galactose 4-epimerase; domain 1
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.90.25.10
catalytic domain: index.html

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

Fructose and mannose metabolism
type: KeggPathway
references: KEGG:MAP00051

NADP+
type: KeggCofactor
references: KEGG:C00006
compound type: amide group
compound type: amine group
compound type: nucleotide
references: CHEBI:18009
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

GDP-mannose
type: KeggSubstrate
references: KEGG:C00096
compound type: amide group
compound type: amine group
compound type: carbohydrate
compound type: nucleotide
references: CHEBI:15820
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

GDP-4-dehydro-6-deoxy-D-mannose
type: KeggProduct
references: KEGG:C01222
compound type: amide group
compound type: amine group
compound type: carbohydrate
compound type: nucleotide
references: CHEBI:16955
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

H2O
type: KeggProduct
references: KEGG:C00001
compound type: H2O
references: CHEBI:15377
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

GDP-4-dehydro-mannose
type: KeggIntermediate
references: KEGG:I00088

GDP-4,5-ene-mannose
type: KeggIntermediate
references: KEGG:I00089

GDP-6-deoxy-4-dehydro-5,6-ene-mannose
type: KeggIntermediate
references: KEGG:I00090

1n7gA01
type: Pdb
references: 1n7g
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1n7g
catalytic residue: ARG 253

1n7gB01
type: Pdb
references: 1n7g
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1n7g
catalytic residue: ARG 253

1n7gC01
type: Pdb
references: 1n7g
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1n7g
catalytic residue: ARG 253

1n7gD01
type: Pdb
references: 1n7g
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1n7g
catalytic residue: ARG 253

1n7hA01
type: Pdb
references: 1n7h
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1n7h
catalytic residue: ARG 253

1n7hB01
type: Pdb
references: 1n7h
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1n7h
catalytic residue: ARG 253

1n7gA02
type: Pdb
references: 1n7g
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1n7g
catalytic residue: SER 162;GLU 164;TYR 185;LYS 189

1n7gB02
type: Pdb
references: 1n7g
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1n7g
catalytic residue: SER 162;GLU 164;TYR 185;LYS 189

1n7gC02
type: Pdb
references: 1n7g
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1n7g
catalytic residue: SER 162;GLU 164;TYR 185;LYS 189

1n7gD02
type: Pdb
references: 1n7g
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1n7g
catalytic residue: SER 162;GLU 164;TYR 185;LYS 189

1n7hA02
type: Pdb
references: 1n7h
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1n7h
catalytic residue: SER 162;GLU 164;TYR 185;LYS 189

1n7hB02
type: Pdb
references: 1n7h
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1n7h
catalytic residue: SER 162;GLU 164;TYR 185;LYS 189

Structural and kinetic analysis of Escherichia coli GDP-mannose 4,6 dehydratase provides insights into the enzyme's catalytic mechanism and regulation by GDP-fucose.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
medline id: 20139699
references: http://www.ncbi.nlm.nih.gov/pubmed/10673432
journal: Structure Fold Des
volume: 8
pages: 123-35
published year: 2000
authors:
  item: Somoza JR
  item: Menon S
  item: Schmidt H
  item: Joseph-McCarthy D
  item: Dessen A
  item: Stahl ML
  item: Somers WS
  item: Sullivan FX
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P0AC88

Identification and characterization of GDP-d-mannose 4,6-dehydratase and GDP-l-fucose snthetase in a GDP-l-fucose biosynthetic gene cluster from Helicobacter pylori.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11444851
journal: Biochem Biophys Res Commun
volume: 285
pages: 364-71
published year: 2001
authors:
  item: Wu B
  item: Zhang Y
  item: Wang PG

Identification of two GDP-6-deoxy-D-lyxo-4-hexulose reductases synthesizing GDP-D-rhamnose in Aneurinibacillus thermoaerophilus L420-91T.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11096116
journal: J Biol Chem
volume: 276
pages: 5577-83
published year: 2001
authors:
  item: Kneidinger B
  item: Graninger M
  item: Adam G
  item: Puchberger M
  item: Kosma P
  item: Zayni S
  item: Messner P

Structure of the MUR1 GDP-mannose 4,6-dehydratase from Arabidopsis thaliana: implications for ligand binding and specificity.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12501186
journal: Biochemistry
volume: 41
pages: 15578-89
published year: 2002
authors:
  item: Mulichak AM
  item: Bonin CP
  item: Reiter WD
  item: Garavito RM
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Crystal structure of a tetrameric GDP-D-mannose 4,6-dehydratase from a bacterial GDP-D-rhamnose biosynthetic pathway.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/14739333
journal: Protein Sci
volume: 13
pages: 529-39
published year: 2004
authors:
  item: Webb NA
  item: Mulichak AM
  item: Lam JS
  item: Rocchetta HL
  item: Garavito RM
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Chemical insights from structural studies of enzymes.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/15493979
journal: Biochem Soc Trans
volume: 32
pages: 647-54
published year: 2004
authors:
  item: Naismith JH

ReferenceForCatalyticMechanism
reference index: 1
reference section: Fig.8, p.131-132
reference step: 3

ReferenceForCatalyticMechanism
reference index: 4
reference section: Fig.1, p.15586
reference step: 3

ReferenceForCatalyticMechanism
reference index: 5
reference section: Fig.4, p.533-535