1MAR: Refined 1.8 Angstroms Structure Of Human Aldose Reductase Complexed With The Potent Inhibitor Zopolrestat

Citation:
Abstract
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.
PDB ID: 1MARDownload
MMDB ID: 56821
PDB Deposition Date: 1993/7/20
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 1MAR: monomeric; determined by author
Molecular Components in 1MAR
Label Count Molecule
Protein (1 molecule)
1
Aldose Reductase(Gene symbol: AKR1B1)
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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