3H4G

Structure of aldehyde reductase holoenzyme in complex with potent aldose reductase inhibitor Fidarestat: Implications for inhibitor binding and selectivity

「2AO0」から置き換えられました

3H4G の概要

• エントリーDOI: 10.2210/pdb3h4g/pdb
• 関連するPDBエントリー: 1PWM 3CV7
• 分子名称: Alcohol dehydrogenase [NADP+], SULFATE ION, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (5 entities in total)
• 機能のキーワード: tim barrel, aldo-keto reductase, ternary complex, nadp, oxidoreductase
• 由来する生物種: Sus scrofa (pigs)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37745.65

構造登録者

Carbone, V.,El-Kabbani, O. (登録日: 2009-04-20, 公開日: 2009-05-05, 最終更新日: 2023-11-01)

主引用文献

El-Kabbani, O.,Carbone, V.,Darmanin, C.,Oka, M.,Mitschler, A.,Podjarny, A.,Schulze-Briese, C.,Chung, R.P.
Structure of aldehyde reductase holoenzyme in complex with the potent aldose reductase inhibitor fidarestat: implications for inhibitor binding and selectivity
J.Med.Chem., 48:5536-5542, 2005

PubMed Abstract: Structure determination of porcine aldehyde reductase holoenzyme in complex with the potent aldose reductase inhibitor fidarestat was carried out to explain the difference in the potency of the inhibitor for aldose and aldehyde reductases. The hydrogen bonds between the active-site residues Tyr50, His113, and Trp114 and fidarestat are conserved in the two enzymes. In aldose reductase, Leu300 forms a hydrogen bond through its main-chain nitrogen atom with the exocyclic amide group of the inhibitor, which when replaced with a Pro in aldehyde reductase, cannot form a hydrogen bond, thus causing a loss in binding energy. Furthermore, in aldehyde reductase, the side chain of Trp220 occupies a disordered split conformation that is not observed in aldose reductase. Molecular modeling and inhibitory activity measurements suggest that the difference in the interaction between the side chain of Trp220 and fidarestat may contribute to the difference in the binding of the inhibitor to the enzymes.

PubMed: 16107153
DOI: 10.1021/jm050412o

実験手法

X-RAY DIFFRACTION (1.85 Å)