2qe0

Thioacylenzyme Intermediate of GAPN from S. Mutans, New Data Integration and Refinement.

spinqualitylabelsall models 2qe0, resolution 2.19Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2qe0 is a 4 chain structure with sequence from Streptococcus mutans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: G3H, NAP Related: 2euh, 2esd Gene: gapN (Streptococcus mutans) Activity: Glyceraldehyde-3-phosphate dehydrogenase (NADP(+)), with EC number 1.2.1.9 Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glyceraldehyde-3-Phosphate Dehydrogenase

Proteopedia Page Contributors and Editors (what is this?)

OCA