1iei

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1iei, resolution 2.5Å

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CRYSTAL STRUCTURE OF HUMAN ALDOSE REDUCTASE COMPLEXED WITH THE INHIBITOR ZENARESTAT.

Overview

The crystal structure of the complex of human recombinant aldose reductase, (AR) with zenarestat, one of its potent inhibitors, has been solved at 2.5, A resolution. Zenarestat fits neatly in the hydrophobic active site and, induces unique and dramatic conformational changes. For example, the, benzene ring of zenarestat occupies a gap in the side chains of Leu300 and, Trp111 that interact directly and forms a CH-pi interaction in the native, holoenzyme. As a result, the benzene ring of the inhibitor and these side, chains form a CH-pi-pi interaction. Such structural information is key to, understanding the mode of action of this class of inhibitors and for, rational design of better therapeutics.

About this Structure

1IEI is a Single protein structure of sequence from Homo sapiens with NAP and ZES as ligands. Active as Aldehyde reductase, with EC number 1.1.1.21 Full crystallographic information is available from OCA.

Reference

The structure of human recombinant aldose reductase complexed with the potent inhibitor zenarestat., Kinoshita T, Miyake H, Fujii T, Takakura S, Goto T, Acta Crystallogr D Biol Crystallogr. 2002 Apr;58(Pt 4):622-6. Epub 2002, Mar 22. PMID:11914486

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