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PDBsum entry 1bsv
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Oxidoreductase PDB id
1bsv

 

 

 

 

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Contents
Protein chain
317 a.a. *
Ligands
NDP
Waters ×84
* Residue conservation analysis
PDB id:
1bsv
Name: Oxidoreductase
Title: Gdp-fucose synthetase from escherichia coli complex with NADPH
Structure: Protein (gdp-fucose synthetase). Chain: a. Synonym: wcag, gdp-4-keto 6-deoxy-mannose 3,5-epimerase 4-reductase. Engineered: yes
Source: Escherichia coli. Organism_taxid: 83333. Strain: k12. Cellular_location: cytoplasm. Gene: wcag. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Dimer (from PDB file)
Resolution:
2.20Å     R-factor:   0.170    
Authors: W.S.Somers,M.L.Stahl,F.X.Sullivan
Key ref:
W.S.Somers et al. (1998). GDP-fucose synthetase from Escherichia coli: structure of a unique member of the short-chain dehydrogenase/reductase family that catalyzes two distinct reactions at the same active site. Structure, 6, 1601-1612. PubMed id: 9862812 DOI: 10.1016/S0969-2126(98)00157-9
Date:
31-Aug-98     Release date:   26-Aug-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P32055  (FCL_ECOLI) -  GDP-L-fucose synthase from Escherichia coli (strain K12)
Seq:
Struc: 		321 a.a.
317 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 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-beta-L-fucose + NADP+ = GDP-4-dehydro-alpha-D-rhamnose + NADPH + H+
GDP-beta-L-fucose
 +
NADP(+)
Bound ligand (Het Group name = NDP)
corresponds exactly 		= GDP-4-dehydro-alpha-D-rhamnose
 + NADPH
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(98)00157-9 Structure 6:1601-1612 (1998)
PubMed id: 9862812  
 
 
GDP-fucose synthetase from Escherichia coli: structure of a unique member of the short-chain dehydrogenase/reductase family that catalyzes two distinct reactions at the same active site.
W.S.Somers, M.L.Stahl, F.X.Sullivan.
 
  ABSTRACT  
 
Background:. In all species examined, GDP-fucose is synthesized from GDP-mannose in a three-step reaction catalyzed by two enzymes, GDP-mannose 4,6 dehydratase and a dual function 3, 5-epimerase-4-reductase named GDP-fucose synthetase. In this latter aspect fucose biosynthesis differs from that of other deoxy and dideoxy sugars, in which the epimerase and reductase activities are present as separate enzymes. Defects in GDP-fucose biosynthesis have been shown to affect nodulation in bacteria, stem development in plants, and are associated with the immune defect leukocyte adhesion deficiency type II in humans. Results:. We have determined the structure of GDP-fucose synthetase from Escherichia coli at 2.2 A resolution. The structure of GDP-fucose synthetase is closely related to that of UDP-galactose 4-epimerase and more distantly to other members of the short-chain dehydrogenase/reductase family. We have also determined the structures of the binary complexes of GDP-fucose synthetase with its substrate NADPH and its product NADP+. The nicotinamide cofactors bind in the syn and anti conformations, respectively. Conclusions:. GDP-fucose synthetase binds its substrate, NADPH, in the proper orientation (syn) for transferring the 4-pro-S hydride of the nicotinamide. We have observed a single binding site in GDP-fucose synthetase for the second substrate, GDP-4-keto,6-deoxy-mannose. This implies that both the epimerization and reduction reactions occur at the same site in the enzyme. As is the case for all members of the short-chain family of dehydrogenase/reductases, GDP-fucose synthetase retains the Ser-Tyr-Lys catalytic triad. We propose that this catalytic triad functions in a mechanistically equivalent manner in both the epimerization and reduction reactions. Additionally, the X-ray structure has allowed us to identify other residues that are potentially required for substrate binding and catalysis.
 
  Selected figure(s)  
 
Figure 6.
Figure 6. A ball-and-stick representation of the GDP-4-keto-6 deoxy-mannose binding model. The proposed binding-site residues are shown with dark bonds and the substrate/NADPH nicotinamide ring is shown with light-grey bonds.
 
  The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 1601-1612) copyright 1998.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19930658 M.H.Serres, A.R.Kerr, T.J.McCormack, and M.Riley (2009).
Evolution by leaps: gene duplication in bacteria.
  Biol Direct, 4, 46.  
  19058170 C.J.Thibodeaux, C.E.Melançon, and H.W.Liu (2008).
Natural-product sugar biosynthesis and enzymatic glycodiversification.
  Angew Chem Int Ed Engl, 47, 9814-9859.  
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.
PDB codes: 2ixc 2ixh 2ixi 2ixj 2ixk 2ixl
16531240 A.H.Ehrensberger, R.A.Elling, and D.K.Wilson (2006).
Structure-guided engineering of xylitol dehydrogenase cosubstrate specificity.
  Structure, 14, 567-575.
PDB code: 1zem
14739333 N.A.Webb, A.M.Mulichak, J.S.Lam, H.L.Rocchetta, and R.M.Garavito (2004).
Crystal structure of a tetrameric GDP-D-mannose 4,6-dehydratase from a bacterial GDP-D-rhamnose biosynthetic pathway.
  Protein Sci, 13, 529-539.
PDB code: 1rpn
14997523 W.Brandt, M.A.Dessoy, M.Fulhorst, W.Gao, M.H.Zenk, and L.A.Wessjohann (2004).
A proposed mechanism for the reductive ring opening of the cyclodiphosphate MEcPP, a crucial transformation in the new DXP/MEP pathway to isoprenoids based on modeling studies and feeding experiments.
  Chembiochem, 5, 311-323.
PDB code: 1ox2
12954627 B.A.Wolucka, and M.Van Montagu (2003).
GDP-mannose 3',5'-epimerase forms GDP-L-gulose, a putative intermediate for the de novo biosynthesis of vitamin C in plants.
  J Biol Chem, 278, 47483-47490.  
12821448 e.l.-.S.E.Habib, J.N.Scarsdale, and K.A.Reynolds (2003).
Biosynthetic origin of hygromycin A.
  Antimicrob Agents Chemother, 47, 2065-2071.  
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.  
11752432 B.A.Wolucka, G.Persiau, J.Van Doorsselaere, M.W.Davey, H.Demol, J.Vandekerckhove, M.Van Montagu, M.Zabeau, and W.Boerjan (2001).
Partial purification and identification of GDP-mannose 3",5"-epimerase of Arabidopsis thaliana, a key enzyme of the plant vitamin C pathway.
  Proc Natl Acad Sci U S A, 98, 14843-14848.  
11306088 E.Maser, G.Xiong, C.Grimm, R.Ficner, and K.Reuter (2001).
3alpha-Hydroxysteroid dehydrogenase/carbonyl reductase from Comamonas testosteroni: biological significance, three-dimensional structure and gene regulation.
  Chem Biol Interact, 130, 707-722.  
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
10848978 J.Benach, S.Atrian, J.Fibla, R.Gonzàlez-Duarte, and R.Ladenstein (2000).
Structure-function relationships in Drosophila melanogaster alcohol dehydrogenase allozymes ADH(S), ADH(F) and ADH(UF), and distantly related forms.
  Eur J Biochem, 267, 3613-3622.  
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.  
11018132 M.Riley, and M.H.Serres (2000).
Interim report on genomics of Escherichia coli.
  Annu Rev Microbiol, 54, 341-411.  
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
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 codes are shown on the right.

 

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