1AE4

ALDEHYDE REDUCTASE COMPLEXED WITH COFACTOR AND INHIBITOR, ALPHA CARBON ATOMS ONLY

1AE4 の概要

• エントリーDOI: 10.2210/pdb1ae4/pdb
• 分子名称: ALDEHYDE REDUCTASE, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, TOLRESTAT (3 entities in total)
• 機能のキーワード: aldo-keto reductase, oxidoreductase, tim-barrel
• 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: 37684.64

構造登録者

El-Kabbani, O. (登録日: 1997-03-05, 公開日: 1998-03-11, 最終更新日: 2024-04-03)

主引用文献

el-Kabbani, O.,Carper, D.A.,McGowan, M.H.,Devedjiev, Y.,Rees-Milton, K.J.,Flynn, T.G.
Studies on the inhibitor-binding site of porcine aldehyde reductase: crystal structure of the holoenzyme-inhibitor ternary complex.
Proteins, 29:186-192, 1997

PubMed Abstract: Aldehyde reductase is an enzyme capable of metabolizing a wide variety of aldehydes to their corresponding alcohols. The tertiary structures of aldehyde reductase and aldose reductase are similar and consist of an alpha/beta-barrel with the active site located at the carboxy terminus of the strands of the barrel. We have determined the X-ray crystal structure of porcine aldehyde reductase holoenzyme in complex with an aldose reductase inhibitor, tolrestat, at 2.4 A resolution to obtain a picture of the binding conformation of inhibitors to aldehyde reductase. Tolrestat binds in the active site pocket of aldehyde reductase and interacts through van der Waals contacts with Arg 312 and Asp 313. The carboxylate group of tolrestat is within hydrogen bonding distance with His 113 and Trp 114. Mutation of Arg 312 to alanine in porcine aldehyde reductase alters the potency of inhibition of the enzyme by aldose reductase inhibitors. Our results indicate that the structure of the inhibitor-binding site of aldehyde reductase differs from that of aldose reductase due to the participation of nonconserved residues in its formation. A major difference is the participation of Arg 312 and Asp 313 in lining the inhibitor-binding site in aldehyde reductase but not in aldose reductase.

PubMed: 9329083
DOI: 10.1002/(SICI)1097-0134(199710)29:2<186::AID-PROT6>3.0.CO;2-B

実験手法

X-RAY DIFFRACTION (2.4 Å)