1mar
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(New page: 200px<br /> <applet load="1mar" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mar, resolution 1.8Å" /> '''REFINED 1.8 ANGSTROM...)
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Revision as of 16:03, 12 November 2007
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REFINED 1.8 ANGSTROMS STRUCTURE OF HUMAN ALDOSE REDUCTASE COMPLEXED WITH THE POTENT INHIBITOR ZOPOLRESTAT
Overview
As the action of aldose reductase (EC 1.1.1.21) is believed to be linked, to the pathogenesis of diabetic complications affecting the nervous, renal, and visual systems, the development of therapeutic agents has, attracted intense effort. We report the refined 1.8 A x-ray structure of, the human holoenzyme complexed with zopolrestat, one of the most potent, noncompetitive inhibitors. The zopolrestat fits snugly in the hydrophobic, active site pocket and induces a hinge-flap motion of two peptide segments, that closes the pocket. Excellent complementarity and affinity are, achieved on inhibitor binding by the formation of 110 contacts (< or = 4, A) with 15 residues (10 hydrophobic), 13 with the NADPH coenzyme and 9, with four water molecules. The structure is key to understanding the mode, of action of this class of inhibitors and for rational design of better, therapeutics.
About this Structure
1MAR is a Single protein structure of sequence from Homo sapiens with NAP and ZST as ligands. Active as Aldehyde reductase, with EC number 1.1.1.21 Full crystallographic information is available from OCA.
Reference
Refined 1.8 A structure of human aldose reductase complexed with the potent inhibitor zopolrestat., Wilson DK, Tarle I, Petrash JM, Quiocho FA, Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9847-51. PMID:8234324
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