2esd
From Proteopedia
OCA (Talk | contribs)
(New page: 200px<br /><applet load="2esd" size="450" color="white" frame="true" align="right" spinBox="true" caption="2esd, resolution 2.55Å" /> '''Crystal Structure of...)
Next diff →
Revision as of 07:59, 21 November 2007
|
Crystal Structure of thioacylenzyme intermediate of an Nadp Dependent Aldehyde Dehydrogenase
Overview
Crystal structures of several members of the nonphosphorylating, CoA-independent aldehyde dehydrogenase (ALDH) family have shown that the, peculiar binding mode of the cofactor to the Rossmann fold results in a, conformational flexibility for the nicotinamide moiety of the cofactor., This has been hypothesized to constitute an essential feature of the, catalytic mechanism because the conformation of the cofactor required for, the acylation step is not appropriate for the deacylation step. In the, present study, the structure of a reaction intermediate of the, E268A-glyceraldehyde 3-phosphate dehydrogenase (GAPN) from Streptococcus, mutans, obtained by soaking the crystals of the enzyme/NADP complex with, the natural substrate, is reported. The substrate is bound covalently in, the four monomers and presents the geometric characteristics expected for, a thioacylenzyme intermediate. Control experiments assessed that reduction, of the coenzyme has occurred within the crystal. The structure reveals, that reduction of the cofactor upon acylation leads to an extensive motion, of the nicotinamide moiety with a flip of the reduced pyridinium ring away, from the active site without significant changes of the protein structure., This event positions the reduced nicotinamide moiety in a pocket that, likely constitutes the exit door for NADPH. Arguments are provided that, the structure reported here constitutes a reasonable picture of the first, thioacylenzyme intermediate characterized thus far in the ALDH family and, that the position of the reduced nicotinamide moiety observed in GAPN is, the one suitable for the deacylation step within all of the, nonphosphorylating CoA-independent ALDH family.
About this Structure
2ESD is a Single protein structure of sequence from Streptococcus mutans with NAP and G3H as ligands. Active as Glyceraldehyde-3-phosphate dehydrogenase (NADP(+)), with EC number 1.2.1.9 Full crystallographic information is available from OCA.
Reference
The first crystal structure of a thioacylenzyme intermediate in the ALDH family: new coenzyme conformation and relevance to catalysis., D'Ambrosio K, Pailot A, Talfournier F, Didierjean C, Benedetti E, Aubry A, Branlant G, Corbier C, Biochemistry. 2006 Mar 7;45(9):2978-86. PMID:16503652
Page seeded by OCA on Wed Nov 21 10:07:05 2007
