EzCatDB: D00513
Related links:    PDB-formatted query search system Fasta-formatted query search system Fasta-formatted query search system

DB codeD00513
RLCP classification9.1050.440000.8010 : Hydride transfer
8.131.164850.131 : Isomerization
5.14.411700.1 : Elimination
9.5010.536210.8010 : Hydride transfer
CATH domainDomain : UDP-galactose 4-epimerase; domain 1Catalytic domain
Domain : Rossmann foldCatalytic domain

CATH domainRelated DB codes (homologues) : Rossmann foldS00543,S00551,S00552,S00553,S00602,S00604,S00605,S00608,S00610,S00625,S00319,S00328,S00329,S00330,S00331,S00332,D00456,D00457,D00458,S00324,S00320,S00325,S00326,S00327,D00459,S00335,S00336,S00334,T00219,S00339,D00001,D00002,D00003,D00005,D00007,D00008,D00010,D00012,D00017,D00018,D00023,D00027,D00028,D00031,D00032,D00033,D00034,D00035,D00037,D00048,D00071,D00476,D00481,D00482,D00490,D00492,D00494,D00545,D00601,D00603,D00604,D00605,D00615,D00845,D00857,D00858,M00161,M00171,M00210,T00002,T00010,T00011,T00015,T00227,T00247,T00408,T00414,D00827,D00262,D00274,D00275,M00035,T00109 : UDP-galactose 4-epimerase; domain 1D00601,D00604,D00262,D00274,D00275

Enzyme Name

Protein nameGDP-mannose 4,6 dehydratase 2GDP-mannose 4,6-dehydratase
guanosine 5'-diphosphate-D-mannose oxidoreductase
guanosine diphosphomannose oxidoreductase
guanosine diphosphomannose 4,6-dehydratase
GDP-D-mannose dehydratase
GDP-D-mannose 4,6-dehydratase
GDP-mannose 4,6-hydro-lyase
GDP-D-mannose dehydratase 2
RefSeqNP_190685.2 (Protein)
NM_114976.3 (DNA/RNA sequence)
PfamPF01370 (Epimerase)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00051Fructose and mannose metabolism

UniProtKB:Accession NumberP93031
Entry nameGMD2_ARATH
ActivityGDP-mannose = GDP-4-dehydro-6-deoxy-D-mannose + H(2)O.
SubunitHomotetramer. Binds to GER1.
Subcellular location

Compound table: links to PDB-related databases & PoSSuM

Typeamide group,amine group,nucleotideamide group,amine group,carbohydrate,nucleotideamide group,amine group,carbohydrate,nucleotideH2O



1n7gA01UnboundUnboundAnalogue:GDR UnboundUnboundUnbound
1n7gB01UnboundUnboundAnalogue:GDR UnboundUnboundUnbound
1n7gC01UnboundUnboundAnalogue:GDR UnboundUnboundUnbound
1n7gD01UnboundUnboundUnbound UnboundUnboundUnbound
1n7hA01UnboundAnalogue:GDPUnbound UnboundUnboundUnbound
1n7hB01UnboundAnalogue:GDPUnbound UnboundUnboundUnbound
1n7gA02Bound:NDPUnboundUnbound UnboundUnboundUnbound
1n7gB02Bound:NDPUnboundUnbound UnboundUnboundUnbound
1n7gC02Bound:NDPUnboundUnbound UnboundUnboundUnbound
1n7gD02Bound:NDPUnboundUnbound UnboundUnboundUnbound
1n7hA02Bound:NDPUnboundUnbound UnboundUnboundUnbound
1n7hB02Bound:NDPUnboundUnbound UnboundUnboundUnbound

Active-site residues
literature [1], [4], [5]
pdbCatalytic residues
1n7gA01ARG 253
1n7gB01ARG 253
1n7gC01ARG 253
1n7gD01ARG 253
1n7hA01ARG 253
1n7hB01ARG 253
1n7gA02SER 162;GLU 164;TYR 185;LYS 189
1n7gB02SER 162;GLU 164;TYR 185;LYS 189
1n7gC02SER 162;GLU 164;TYR 185;LYS 189
1n7gD02SER 162;GLU 164;TYR 185;LYS 189
1n7hA02SER 162;GLU 164;TYR 185;LYS 189
1n7hB02SER 162;GLU 164;TYR 185;LYS 189

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]Fig.8, p.131-1323
[4]Fig.1, p.155863
[5]Fig.4, p.533-535

Medline ID20139699
PubMed ID10673432
JournalStructure Fold Des
AuthorsSomoza JR, Menon S, Schmidt H, Joseph-McCarthy D, Dessen A, Stahl ML, Somers WS, Sullivan FX
TitleStructural and kinetic analysis of Escherichia coli GDP-mannose 4,6 dehydratase provides insights into the enzyme's catalytic mechanism and regulation by GDP-fucose.
Related PDB1db3
Related UniProtKBP0AC88
PubMed ID11444851
JournalBiochem Biophys Res Commun
AuthorsWu B, Zhang Y, Wang PG
TitleIdentification 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.
PubMed ID11096116
JournalJ Biol Chem
AuthorsKneidinger B, Graninger M, Adam G, Puchberger M, Kosma P, Zayni S, Messner P
TitleIdentification of two GDP-6-deoxy-D-lyxo-4-hexulose reductases synthesizing GDP-D-rhamnose in Aneurinibacillus thermoaerophilus L420-91T.
PubMed ID12501186
AuthorsMulichak AM, Bonin CP, Reiter WD, Garavito RM
TitleStructure of the MUR1 GDP-mannose 4,6-dehydratase from Arabidopsis thaliana: implications for ligand binding and specificity.
Related PDB1n7g,1n7h
PubMed ID14739333
JournalProtein Sci
AuthorsWebb NA, Mulichak AM, Lam JS, Rocchetta HL, Garavito RM
TitleCrystal structure of a tetrameric GDP-D-mannose 4,6-dehydratase from a bacterial GDP-D-rhamnose biosynthetic pathway.
Related PDB1rpn
PubMed ID15493979
JournalBiochem Soc Trans
AuthorsNaismith JH
TitleChemical insights from structural studies of enzymes.

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, 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 intermediate might modulate the pKa of Glu164 as a general acid.
(C1) Glu164 acts as a general acid to protonate O6 hydroxyl group, to release a water molecule, and to form the 4-keto-5,6-ene intermediate from the enol/enolate intermediate.
(D) Hydride transfer from NAD(P)H to C6 atom of the intermediate:
(D0) A slight rotation of the hexose ring of intermediate might be necessary for the reaction. Lys189 modulates the activity (or pKa) of Tyr185 via 2'-hydroxyl group of NADP, along with the N1 atom of the nicotinamide group in NADP.
(D1) Hydride transfer from NAD(P)H to C6 atom of the hexose ring in the intermediate. Meanwhile, a general acid must protonate the C5 atom of the hexose. According to the literature [5], Ser162, which is corresponding to Thr126 (of 1rpn in D00543), seems to be positioned to play a role as a general acid. Since this residue is close enough to Tyr185, Tyr185 might act as a general acid via Thr126 to protonate the C5 atom.


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
© Biotechnology Research Institute for Drug Discovery, AIST, 2015-2016 All Rights Reserved.
© Computational Biology Research Center, AIST, 2004-2016 All Rights Reserved.