1bsv
|
GDP-FUCOSE SYNTHETASE FROM ESCHERICHIA COLI COMPLEX WITH NADPH
OverviewOverview
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.
About this StructureAbout this Structure
1BSV is a Single protein structure of sequence from Escherichia coli with NDP as ligand. Full crystallographic information is available from OCA.
ReferenceReference
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., Somers WS, Stahl ML, Sullivan FX, Structure. 1998 Dec 15;6(12):1601-12. PMID:9862812
Page seeded by OCA on Tue Nov 20 11:53:44 2007