3BCJ

Crystal structure of Aldose Reductase complexed with 2S4R (Stereoisomer of Fidarestat, 2S4S) at 0.78 A

3BCJ の概要

• エントリーDOI: 10.2210/pdb3bcj/pdb
• 関連するPDBエントリー: 1PWM 1X98
• 分子名称: Aldose reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, CITRIC ACID, ... (5 entities in total)
• 機能のキーワード: aldo-keto reductases, diabetes, drug design, polyl pathway, acetylation, cataract, cytoplasm, nadp, oxidoreductase, polymorphism
• 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: 37113.09

構造登録者

Zhao, H.T.,El-Kabbani, O. (登録日: 2007-11-13, 公開日: 2008-04-08, 最終更新日: 2023-11-01)

主引用文献

Zhao, H.T.,Hazemann, I.,Mitschler, A.,Carbone, V.,Joachimiak, A.,Ginell, S.,Podjarny, A.,El-Kabbani, O.
Unusual Binding Mode of the 2S4R Stereoisomer of the Potent Aldose Reductase Cyclic Imide Inhibitor Fidarestat (2S4S) in the 15 K Crystal Structure of the Ternary Complex Refined at 0.78 A Resolution: Implications for the Inhibition Mechanism
J.Med.Chem., 51:1478-1481, 2008

PubMed Abstract: The structure of human aldose reductase in complex with the 2 S4 R stereoisomer of the potent inhibitor Fidarestat ((2 S,4 S)-6-fluoro-2',5'-dioxospiro-[chroman-4,4'-imidazoline]-2-carboxamide) was determined at 15 K and a resolution of 0.78 A. The structure of the complex provides experimental evidence for the inhibition mechanism in which Fidarestat is initially bound neutral and then becomes negatively charged by donating the proton at the 1'-position nitrogen of the cyclic imide ring to the N2 atom of the catalytic His110.

PubMed: 18284183
DOI: 10.1021/jm701514k

実験手法

X-RAY DIFFRACTION (0.78 Å)