1pr9
From Proteopedia
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Human L-Xylulose Reductase Holoenzyme
Overview
L-Xylulose reductase (XR), an enzyme in the uronate cycle of glucose, metabolism, belongs to the short-chain dehydrogenase/reductase (SDR), superfamily. Among the SDR enzymes, XR shows the highest sequence identity, (67%) with mouse lung carbonyl reductase (MLCR), but the two enzymes show, different substrate specificities. The crystal structure of human XR in, complex with reduced nicotinamide adenine dinucleotide phosphate (NADPH), was determined at 1.96 A resolution by using the molecular replacement, method and the structure of MLCR as the search model. Features unique to, human XR include electrostatic interactions between the N-terminal, residues of subunits related by the P-axis, termed according to SDR, convention, and an interaction between the hydroxy group of Ser185 and the, pyrophosphate of NADPH. Furthermore, identification of the residues lining, the active site of XR (Cys138, Val143, His146, Trp191, and Met200), together with a model structure of XR in complex with L-xylulose, revealed, structural differences with other members of the SDR family, which may, account for the distinct substrate specificity of XR. The residues, comprising a recently proposed catalytic tetrad in the SDR enzymes are, conserved in human XR (Asn107, Ser136, Tyr149, and Lys153). To examine the, role of Asn107 in the catalytic mechanism of human XR, mutant forms (N107D, and N107L) were prepared. The two mutations increased K(m) for the, substrate (>26-fold) and K(d) for NADPH (95-fold), but only the N107L, mutation significantly decreased k(cat) value. These results suggest that, Asn107 plays a critical role in coenzyme binding rather than in the, catalytic mechanism.
About this Structure
1PR9 is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as L-xylulose reductase, with EC number 1.1.1.10 Full crystallographic information is available from OCA.
Reference
Crystal structure of human L-xylulose reductase holoenzyme: probing the role of Asn107 with site-directed mutagenesis., El-Kabbani O, Ishikura S, Darmanin C, Carbone V, Chung RP, Usami N, Hara A, Proteins. 2004 May 15;55(3):724-32. PMID:15103634
Page seeded by OCA on Fri Feb 15 16:41:03 2008
