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Oxidoreductase PDB id
1bws
Jmol
Contents
Protein chain
314 a.a. *
Ligands
NDP
Waters ×109
* Residue conservation analysis
PDB id:
1bws
Name: Oxidoreductase
Title: Crystal structure of gdp-4-keto-6-deoxy-d-mannose epimerase/ from escherichia coli a key enzyme in the biosynthesis of g fucose
Structure: Protein (gdp-4-keto-6-deoxy-d-mannose epimerase/r chain: a. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.20Å     R-factor:   0.202     R-free:   0.287
Authors: M.Rizzi,M.Tonetti,A.D.Flora,M.Bolognesi
Key ref:
M.Rizzi et al. (1998). GDP-4-keto-6-deoxy-D-mannose epimerase/reductase from Escherichia coli, a key enzyme in the biosynthesis of GDP-L-fucose, displays the structural characteristics of the RED protein homology superfamily. Structure, 6, 1453-1465. PubMed id: 9817848 DOI: 10.1016/S0969-2126(98)00144-0
Date:
25-Sep-98     Release date:   13-Jan-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P32055  (FCL_ECOLI) -  GDP-L-fucose synthase
Seq:
Struc: 		321 a.a.
314 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.1.1.1.271  - GDP-L-fucose synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		GDP-L-Fucose and GDP-mannose Biosynthesis
      Reaction: GDP-L-fucose + NADP+ = GDP-4-dehydro-6-deoxy-D-mannose + NADPH
GDP-L-fucose
 +
NADP(+)
Bound ligand (Het Group name = NDP)
corresponds exactly 		= GDP-4-dehydro-6-deoxy-D-mannose
 + NADPH
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     metabolic process   5 terms 
  Biochemical function     catalytic activity     6 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(98)00144-0 Structure 6:1453-1465 (1998)
PubMed id: 9817848  
 
 
GDP-4-keto-6-deoxy-D-mannose epimerase/reductase from Escherichia coli, a key enzyme in the biosynthesis of GDP-L-fucose, displays the structural characteristics of the RED protein homology superfamily.
M.Rizzi, M.Tonetti, P.Vigevani, L.Sturla, A.Bisso, A.D.Flora, D.Bordo, M.Bolognesi.
 
  ABSTRACT  
 
BACKGROUND: The process of guanosine 5'-diphosphate L-fucose (GDP-L-fucose) biosynthesis is conserved throughout evolution from prokaryotes to man. In animals, GDP-L-fucose is the substrate of fucosyltransferases that participate in the biosynthesis and remodeling of glycoconjugates, including ABH blood group and Lewis-system antigens. The 'de novo' pathway of GDP-L-fucose biosynthesis from GDP-D-mannose involves a GDP-D-mannose 4,6 dehydratase (GMD) and a GDP-4-keto-6-deoxy-D-mannose epimerase/reductase (GMER). Neither of the catalytic mechanisms nor the three-dimensional structures of the two enzymes has been elucidated yet. The severe leukocyte adhesion deficiency (LAD) type II genetic syndrome is known to result from deficiencies in this de novo pathway. RESULTS: The crystal structures of apo- and holo-GMER have been determined at 2.1 A and 2.2 A resolution, respectively. Each subunit of the homodimeric (2 x 34 kDa) enzyme is composed of two domains. The N-terminal domain, a six-stranded Rossmann fold, binds NADP+; the C-terminal domain (about 100 residues) displays an alpha/beta topology. NADP+ interacts with residues Arg12 and Arg36 at the adenylic ribose phosphate; moreover, a protein loop based on the Gly-X-X-Gly-X-X-Gly motif (where X is any amino acid) stabilizes binding of the coenzyme diphosphate bridge. The nicotinamide and the connected ribose ring are located close to residues Ser107, Tyr136 and Lys140, the putative GMER active-site center. CONCLUSIONS: The GMER fold is reminiscent of that observed for UDP-galactose epimerase (UGE) from Escherichia coli. Consideration of the enzyme fold and of its main structural features allows assignment of GMER to the reductase-epimerase-dehydrogenase (RED) enzyme homology superfamily, to which short-chain dehydrogenase/reductases (SDRs) also belong. The location of the NADP+ nicotinamide ring at an interdomain cleft is compatible with substrate binding in the C-terminal domain.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Stereo images displaying the structural overlay of Ca backbones of: (a) GMER (green) and UGE (magenta); (b) GMER and mouse lung carbonyl reductase (blue); (c) GMER and the Salmonella typhimurium glucose/galactose-binding protein (red).
 
  The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 1453-1465) copyright 1998.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19058030 Y.Kim, H.Li, T.A.Binkowski, D.Holzle, and A.Joachimiak (2009).
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17046787 C.Dong, L.L.Major, V.Srikannathasan, J.C.Errey, M.F.Giraud, J.S.Lam, M.Graninger, P.Messner, M.R.McNeil, R.A.Field, C.Whitfield, and J.H.Naismith (2007).
RmlC, a C3' and C5' carbohydrate epimerase, appears to operate via an intermediate with an unusual twist boat conformation.
  J Mol Biol, 365, 146-159.
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17950751 J.D.King, N.J.Harmer, A.Preston, C.M.Palmer, M.Rejzek, R.A.Field, T.L.Blundell, and D.J.Maskell (2007).
Predicting protein function from structure--the roles of short-chain dehydrogenase/reductase enzymes in Bordetella O-antigen biosynthesis.
  J Mol Biol, 374, 749-763.
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12788945 G.J.Tanner, K.T.Francki, S.Abrahams, J.M.Watson, P.J.Larkin, and A.R.Ashton (2003).
Proanthocyanidin biosynthesis in plants. Purification of legume leucoanthocyanidin reductase and molecular cloning of its cDNA.
  J Biol Chem, 278, 31647-31656.  
  12860704 H.A.Thompson, T.A.Hoover, M.H.Vodkin, and E.I.Shaw (2003).
Do chromosomal deletions in the lipopolysaccharide biosynthetic regions explain all cases of phase variation in Coxiella burnetii strains? An update.
  Ann N Y Acad Sci, 990, 664-670.  
12004063 C.Creuzenet, R.V.Urbanic, and J.S.Lam (2002).
Structure-function studies of two novel UDP-GlcNAc C6 dehydratases/C4 reductases. Variation from the SYK dogma.
  J Biol Chem, 277, 26769-26778.  
11737200 N.Järvinen, M.Mäki, J.Räbinä, C.Roos, P.Mattila, and R.Renkonen (2001).
Cloning and expression of Helicobacter pylori GDP-l-fucose synthesizing enzymes (GMD and GMER) in Saccharomyces cerevisiae.
  Eur J Biochem, 268, 6458-6464.  
  10896473 A.M.Deacon, Y.S.Ni, W.G.Coleman, and S.E.Ealick (2000).
The crystal structure of ADP-L-glycero-D-mannoheptose 6-epimerase: catalysis with a twist.
  Structure, 8, 453-462.
PDB code: 1eq2
  10673432 J.R.Somoza, S.Menon, H.Schmidt, D.Joseph-McCarthy, A.Dessen, M.L.Stahl, W.S.Somers, and F.X.Sullivan (2000).
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.
  Structure, 8, 123-135.
PDB code: 1db3
11114506 M.F.Giraud, and J.H.Naismith (2000).
The rhamnose pathway.
  Curr Opin Struct Biol, 10, 687-696.  
10557279 A.M.Mulichak, M.J.Theisen, B.Essigmann, C.Benning, and R.M.Garavito (1999).
Crystal structure of SQD1, an enzyme involved in the biosynthesis of the plant sulfolipid headgroup donor UDP-sulfoquinovose.
  Proc Natl Acad Sci U S A, 96, 13097-13102.
PDB code: 1qrr
10666586 M.F.Giraud, H.J.McMiken, G.A.Leonard, P.Messner, C.Whitfield, and J.H.Naismith (1999).
Overexpression, purification, crystallization and preliminary structural study of dTDP-6-deoxy-L-lyxo-4-hexulose reductase (RmlD), the fourth enzyme of the dTDP-L-rhamnose synthesis pathway, from Salmonella enterica serovar Typhimurium.
  Acta Crystallogr D Biol Crystallogr, 55, 2043-2046.  
10455186 M.Graninger, B.Nidetzky, D.E.Heinrichs, C.Whitfield, and P.Messner (1999).
Characterization of dTDP-4-dehydrorhamnose 3,5-epimerase and dTDP-4-dehydrorhamnose reductase, required for dTDP-L-rhamnose biosynthesis in Salmonella enterica serovar Typhimurium LT2.
  J Biol Chem, 274, 25069-25077.  
10480878 S.Menon, M.Stahl, R.Kumar, G.Y.Xu, and F.Sullivan (1999).
Stereochemical course and steady state mechanism of the reaction catalyzed by the GDP-fucose synthetase from Escherichia coli.
  J Biol Chem, 274, 26743-26750.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.