1ef3
From Proteopedia
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FIDARESTAT BOUND TO HUMAN ALDOSE REDUCTASE
Overview
The absolute configuration of the aldose reductase (AR) inhibitor, (+)-(2S,4S)-6-fluoro-2',5'-dioxospiro inverted question markchroman-4, 4'-imidazolidine-2-carboxamide (fidarestat), was established indirectly by, single-crystal X-ray analysis of (+)-(2S, 4S)-8-bromo-6-fluoro-2',5'-dioxospiro inverted question markchroman-4, 4'-imidazolidine-2-carboxylic acid (1). The crystal structure of human AR, complexed with fidarestat was determined, and the specific inhibition, activity was discussed on the basis of the three-dimensional interactions, between them. The structure clarified that fidarestat was located in the, active site by hydrophilic and hydrophobic interactions and that the, carbamoyl group of fidarestat was a very effective substituent for, affinity to AR and for selectivity between AR and aldehyde reductase, (AHR). Explanations for the differences between the observed activities of, fidarestat and its stereoisomer 2 were suggested by computer modeling.
About this Structure
1EF3 is a Single protein structure of sequence from Homo sapiens with NAP and FID as ligands. Active as Aldehyde reductase, with EC number 1.1.1.21 Full crystallographic information is available from OCA.
Reference
A potent aldose reductase inhibitor, (2S,4S)-6-fluoro-2', 5'-dioxospiro[chroman-4,4'-imidazolidine]-2-carboxamide (Fidarestat): its absolute configuration and interactions with the aldose reductase by X-ray crystallography., Oka M, Matsumoto Y, Sugiyama S, Tsuruta N, Matsushima M, J Med Chem. 2000 Jun 15;43(12):2479-83. PMID:10882376
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