1MAR

REFINED 1.8 ANGSTROMS STRUCTURE OF HUMAN ALDOSE REDUCTASE COMPLEXED WITH THE POTENT INHIBITOR ZOPOLRESTAT

1MAR の概要

• エントリーDOI: 10.2210/pdb1mar/pdb
• 分子名称: ALDOSE REDUCTASE, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 3,4-DIHYDRO-4-OXO-3-((5-TRIFLUOROMETHYL-2-BENZOTHIAZOLYL)METHYL)-1-PHTHALAZINE ACETIC ACID (3 entities in total)
• 機能のキーワード: oxidoreductase(nadp)
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P15121
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36929.93

構造登録者

Wilson, D.K.,Quiocho, F.A. (登録日: 1993-07-20, 公開日: 1995-07-20, 最終更新日: 2024-02-14)

主引用文献

Wilson, D.K.,Tarle, I.,Petrash, J.M.,Quiocho, F.A.
Refined 1.8 A structure of human aldose reductase complexed with the potent inhibitor zopolrestat.
Proc.Natl.Acad.Sci.USA, 90:9847-9851, 1993

PubMed 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.

PubMed: 8234324
DOI: 10.1073/pnas.90.21.9847

実験手法

X-RAY DIFFRACTION (1.8 Å)