4QX4

Human Aldose Reductase complexed with a ligand with a new scaffold at 1.26 A

4QX4 の概要

• エントリーDOI: 10.2210/pdb4qx4/pdb
• 関連するPDBエントリー: 1US0
• 分子名称: Aldose reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, (3-thioxo-2,3-dihydro-5H-[1,2,4]triazino[5,6-b]indol-5-yl)acetic acid, ... (4 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: 37162.29

構造登録者

Rechlin, C.,Heine, A.,Klebe, G. (登録日: 2014-07-18, 公開日: 2015-04-01, 最終更新日: 2023-09-20)

主引用文献

Stefek, M.,Soltesova Prnova, M.,Majekova, M.,Rechlin, C.,Heine, A.,Klebe, G.
Identification of novel aldose reductase inhibitors based on carboxymethylated mercaptotriazinoindole scaffold.
J.Med.Chem., 58:2649-2657, 2015

PubMed Abstract: Fifteen compounds, sharing an indole-1-acetic acid moiety as a common fragment, were selected from commercial databases for testing aldose reductase inhibition. 3-Mercapto-5H-1,2,4-triazino[5,6-b]indole-5-acetic acid (13) was the most promising inhibitor, with an IC50 in the submicromolar range and high selectivity, relative to aldehyde reductase. The crystal structure of aldose reductase complexed with 13 revealed an interaction pattern explaining its high affinity. Physicochemical parameters underline the excellent "leadlikeness" of 13 as a promising candidate for further structure optimizations.

PubMed: 25695864
DOI: 10.1021/jm5015814

実験手法

X-RAY DIFFRACTION (1.259 Å)