1db3
From Proteopedia
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'''E.COLI GDP-MANNOSE 4,6-DEHYDRATASE''' | '''E.COLI GDP-MANNOSE 4,6-DEHYDRATASE''' | ||
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[[Category: Somoza, J R.]] | [[Category: Somoza, J R.]] | ||
[[Category: Sullivan, F X.]] | [[Category: Sullivan, F X.]] | ||
| - | [[Category: | + | [[Category: Dehydratase]] |
| - | [[Category: | + | [[Category: Gdp-fucose]] |
| - | [[Category: | + | [[Category: Gdp-mannose]] |
| - | [[Category: | + | [[Category: Nadp]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 13:38:59 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 10:38, 2 May 2008
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. 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 Fri May 2 13:38:59 2008
