1IEI

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

Summary for 1IEI

• Entry DOI: 10.2210/pdb1iei/pdb
• Descriptor: ALDOSE REDUCTASE, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, [3-(4-BROMO-2-FLUORO-BENZYL)-7-CHLORO-2,4-DIOXO-3,4-DIHYDRO-2H-QUINAZOLIN-1-YL]-ACETIC ACID, ... (4 entities in total)
• Functional Keywords: protein-inhibitor complex, nadp, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P15121
• Total number of polymer chains: 1
• Total formula weight: 37083.38

Authors

Kinoshita, T.,Miyake, H.,Fujii, T.,Takakura, S.,Goto, T. (deposition date: 2001-04-09, release date: 2002-04-10, Last modification date: 2024-03-13)

Primary citation

Kinoshita, T.,Miyake, H.,Fujii, T.,Takakura, S.,Goto, T.
The structure of human recombinant aldose reductase complexed with the potent inhibitor zenarestat.
Acta Crystallogr.,Sect.D, 58:622-626, 2002

PubMed Abstract: 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.

PubMed: 11914486
DOI: 10.1107/S0907444902002378

Experimental method

X-RAY DIFFRACTION (2.5 Å)