4JIR

Crystal Structure Of Aldose Reductase (AKR1B1) Complexed With NADP+ And Epalrestat

4JIR の概要

• エントリーDOI: 10.2210/pdb4jir/pdb
• 関連するPDBエントリー: 4GQ0 4GQG 4I5X 4JIH 4JII
• 分子名称: Aldose reductase, {5-[(2E)-2-methyl-3-phenylprop-2-en-1-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl}acetic acid, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: tim barrel, oxidoreductase, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 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: 37153.27

構造登録者

Zhang, L.,Zheng, X.,Zhang, H.,Zhao, Y.,Chen, K.,Zhai, J.,Hu, X. (登録日: 2013-03-06, 公開日: 2013-10-23, 最終更新日: 2024-02-28)

主引用文献

Zhang, L.,Zhang, H.,Zhao, Y.,Li, Z.,Chen, S.,Zhai, J.,Chen, Y.,Xie, W.,Wang, Z.,Li, Q.,Zheng, X.,Hu, X.
Inhibitor selectivity between aldo-keto reductase superfamily members AKR1B10 and AKR1B1: Role of Trp112 (Trp111).
Febs Lett., 587:3681-3686, 2013

PubMed Abstract: The antineoplastic target aldo-keto reductase family member 1B10 (AKR1B10) and the critical polyol pathway enzyme aldose reductase (AKR1B1) share high structural similarity. Crystal structures reported here reveal a surprising Trp112 native conformation stabilized by a specific Gln114-centered hydrogen bond network in the AKR1B10 holoenzyme, and suggest that AKR1B1 inhibitors could retain their binding affinities toward AKR1B10 by inducing Trp112 flip to result in an "AKR1B1-like" active site in AKR1B10, while selective AKR1B10 inhibitors can take advantage of the broader active site of AKR1B10 provided by the native Trp112 side-chain orientation.

PubMed: 24100137
DOI: 10.1016/j.febslet.2013.09.031

実験手法

X-RAY DIFFRACTION (2 Å)