3FX4

Porcine aldehyde reductase in ternary complex with inhibitor

3FX4 の概要

• エントリーDOI: 10.2210/pdb3fx4/pdb
• 関連するPDBエントリー: 2AO0 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, acetylation, nadp, oxidoreductase
• 由来する生物種: Sus scrofa (Pig)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38025.88

構造登録者

Carbone, V.,El-Kabbani, O. (登録日: 2009-01-20, 公開日: 2009-12-22, 最終更新日: 2023-11-01)

主引用文献

Carbone, V.,Giglio, M.,Chung, R.,Huyton, T.,Adams, J.,Maccari, R.,Ottana, R.,Hara, A.,El-Kabbani, O.
Structure of aldehyde reductase in ternary complex with a 5-arylidene-2,4-thiazolidinedione aldose reductase inhibitor.
Eur.J.Med.Chem., 45:1140-1145, 2010

PubMed Abstract: The structure of aldehyde reductase (ALR1) in ternary complex with the coenzyme NADPH and [5-(3-carboxymethoxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid (CMD), a potent inhibitor of aldose reductase (ALR2), was determined at 1.99A resolution. The partially disordered inhibitor formed a tight network of hydrogen bonds with the active site residues (Tyr50 and His113) and coenzyme. Molecular modelling calculations and inhibitory activity measurements of CMD and [5-(3-hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid (HMD) indicated that pi-stacking interactions with several conserved active site tryptophan residues and hydrogen-bonding interactions with the non-conserved C-terminal residue Leu300 in ALR2 (Pro301 in ALR1) contributed to inhibitor selectivity. In particular for the potent inhibitor CMD, the rotameric state of the conserved residue Trp219 (Trp220 in ALR1) is important in forming a pi-stacking interaction with the inhibitor in ALR2 and contributes to the difference in the binding of the inhibitor to the enzymes.

PubMed: 20036445
DOI: 10.1016/j.ejmech.2009.12.019

実験手法

X-RAY DIFFRACTION (1.99 Å)