1c9w

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spinqualitylabelsall models 1c9w, resolution 2.4Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CHO REDUCTASE WITH NADP+

Overview

Chinese hamster ovary (CHO) reductase is an enzyme belonging to the, aldo-keto reductase (AKR) superfamily that is induced by the, aldehyde-containing protease inhibitor ALLN (Inoue, Sharma, Schimke, et, al., J Biol Chem 1993;268: 5894). It shows 70% sequence identity to human, aldose reductase (Hyndman, Takenoshita, Vera, et al., J Biol Chem, 1997;272:13286), which is a target for drug design because of its, implication in diabetic complications. We have determined the crystal, structure of CHO reductase complexed with nicotinamide adenine, dinucleotide phosphate (NADP)+ to 2.4 A resolution. Similar to aldose, reductase and other AKRs, CHO reductase is an alpha/beta TIM barrel enzyme, with cofactor bound in an extended conformation. All key residues involved, in cofactor binding are conserved with respect to other AKR members. CHO, reductase shows a high degree of sequence identity (91%) with another AKR, member, FR-1 (mouse fibroblast growth factor-regulated protein), especially around the variable C-terminal end of the protein and has a, similar substrate binding pocket that is larger than that of aldose, reductase. However, there are distinct differences that can account for, differences in substrate specificity. Trp111, which lies horizontal to the, substrate pocket in all other AKR members is perpendicular in CHO, reductase and is accompanied by movement of Leu300. This coupled with, movement of loops A, B, and C away from the active site region accounts, for the ability of CHO reductase to bind larger substrates. The position, of Trp219 is significantly altered with respect to aldose reductase and, appears to release Cys298 from steric constraints. These studies show that, AKRs such as CHO reductase are excellent models for examining the effects, of subtle changes in amino acid sequence and alignment on binding and, catalysis.

About this Structure

1C9W is a Single protein structure of sequence from Cricetulus griseus with NAP as ligand. Active as Alcohol dehydrogenase (NADP(+)), with EC number 1.1.1.2 Full crystallographic information is available from OCA.

Reference

Crystal structure of CHO reductase, a member of the aldo-keto reductase superfamily., Ye Q, Hyndman D, Li X, Flynn TG, Jia Z, Proteins. 2000 Jan 1;38(1):41-8. PMID:10651037

Page seeded by OCA on Tue Nov 20 12:17:49 2007