2o2r

From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models 2o2r, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of the C-terminal domain of rat 10'formyltetrahydrofolate dehydrogenase in complex with NADPH

Overview

10-Formyltetrahydrofolate dehydrogenase (FDH) catalyzes an NADP+-dependent, dehydrogenase reaction resulting in conversion of, 10-formyltetrahydrofolate to tetrahydrofolate and CO2. This reaction is a, result of the concerted action of two catalytic domains of FDH, the, amino-terminal hydrolase domain and the carboxyl-terminal aldehyde, dehydrogenase domain. In addition to participation in the overall FDH, mechanism, the C-terminal domain is capable of NADP+-dependent oxidation, of short chain aldehydes to their corresponding acids. We have determined, the crystal structure of the C-terminal domain of FDH and its complexes, with oxidized and reduced forms of NADP. Compared to other members of the, ALDH family, FDH demonstrates a new mode of binding of the 2'-phosphate, group of NADP via a water-mediated contact with Gln600 that may contribute, to the specificity of the enzyme for NADP over NAD. The structures also, suggest how Glu673 can act as a general base in both acylation and, deacylation steps of the reaction. In the apo structure, the general base, Glu673 is positioned optimally for proton abstraction from the sulfur atom, of Cys707. Upon binding of NADP+, the side chain of Glu673 is displaced, from the active site by the nicotinamide ring and contacts a chain of, highly ordered water molecules that may represent a pathway for, translocation of the abstracted proton from Glu673 to the solvent. When, reduced, the nicotinamide ring of NADP is displaced from the active site, restoring the contact between Cys707 and Glu673 and allowing the latter to, activate the hydrolytic water molecule in deacylation.

About this Structure

2O2R is a Single protein structure of sequence from Rattus norvegicus with SO4, NDP and GOL as ligands. Active as Formyltetrahydrofolate dehydrogenase, with EC number 1.5.1.6 Full crystallographic information is available from OCA.

Reference

Crystal Structures of the Carboxyl Terminal Domain of Rat 10-Formyltetrahydrofolate Dehydrogenase: Implications for the Catalytic Mechanism of Aldehyde Dehydrogenases., Tsybovsky Y, Donato H, Krupenko NI, Davies C, Krupenko SA, Biochemistry. 2007 Feb 16;. PMID:17302434

Page seeded by OCA on Wed Nov 21 13:02:27 2007