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1db3
From Proteopedia
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E.COLI GDP-MANNOSE 4,6-DEHYDRATASE
Overview
Background: GDP-mannose 4,6 dehydratase (GMD) catalyzes the conversion of, GDP-(D)-mannose to GDP-4-keto, 6-deoxy-(D)-mannose. This is the first and, regulatory step in the de novo biosynthesis of GDP-(L)-fucose. Fucose, forms part of a number of glycoconjugates, including the ABO blood groups, and the selectin ligand sialyl Lewis X. Defects in GDP-fucose metabolism, have been linked to leukocyte adhesion deficiency type II (LADII)., Results: The structure of the GDP-mannose 4,6 dehydratase apo enzyme has, been determined and refined using data to 2.3 A resolution. GMD is a, homodimeric protein with each monomer composed of two domains. The larger, N-terminal domain binds the NADP(H) cofactor in a classical Rossmann fold, and the C-terminal domain harbors the sugar-nucleotide binding site. We, have determined the GMD dissociation constants for NADP, NADPH and, GDP-mannose. Each GMD monomer binds one cofactor and one substrate, molecule, suggesting that both subunits are catalytically competent., GDP-fucose acts as a competitive inhibitor, suggesting that it binds to, the same site as GDP-mannose, providing a mechanism for the feedback, inhibition of fucose biosynthesis. Conclusions: The X-ray structure of GMD, reveals that it is a member of the short-chain dehydrogenase/reductase, (SDR) family of proteins. We have modeled the binding of NADP and, GDP-mannose to the enzyme and mutated four of the active-site residues to, determine their function. The combined modeling and mutagenesis data, suggests that at position 133 threonine substitutes serine as part of the, serine-tyrosine-lysine catalytic triad common to the SDR family and Glu, 135 functions as an active-site base.
About this Structure
1DB3 is a Single protein structure of sequence from Escherichia coli. Active as GDP-mannose 4,6-dehydratase, with EC number 4.2.1.47 Full crystallographic information is available from OCA.
Reference
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., Somoza JR, Menon S, Schmidt H, Joseph-McCarthy D, Dessen A, Stahl ML, Somers WS, Sullivan FX, Structure. 2000 Feb 15;8(2):123-35. PMID:10673432
Page seeded by OCA on Tue Nov 20 13:08:06 2007
