2VLE

The structure of daidzin, a naturally occurring anti alcohol- addiction agent, in complex with human mitochondrial aldehyde dehydrogenase

「1OF7」から置き換えられました

2VLE の概要

• エントリーDOI: 10.2210/pdb2vle/pdb
• 関連するPDBエントリー: 1CW3 1NZW 1NZX 1NZZ 1O00 1O01 1O02 1O04 1O05 1ZUM
• 分子名称: ALDEHYDE DEHYDROGENASE, MITOCHONDRIAL, DAIDZIN (3 entities in total)
• 機能のキーワード: transit peptide, aldehyde dehydrogenase, nad, daidzin, acetylation, polymorphism, mitochondrion, alcohol abuse, oxidoreductase
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Mitochondrion matrix: P05091
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 435091.74

構造登録者

Lowe, E.D.,Gao, G.Y.,Johnson, L.N.,Keung, W.M. (登録日: 2008-01-13, 公開日: 2008-08-19, 最終更新日: 2023-12-13)

主引用文献

Lowe, E.D.,Gao, G.Y.,Johnson, L.N.,Keung, W.M.
Structure of Daidzin, a Naturally Occurring Anti-Alcohol-Addiction Agent, in Complex with Human Mitochondrial Aldehyde Dehydrogenase.
J.Med.Chem., 51:4482-, 2008

PubMed Abstract: The ALDH2*2 gene encoding the inactive variant form of mitochondrial aldehyde dehydrogenase (ALDH2) protects nearly all carriers of this gene from alcoholism. Inhibition of ALDH2 has hence become a possible strategy to treat alcoholism. The natural product 7-O-glucosyl-4'-hydroxyisoflavone (daidzin), isolated from the kudzu vine ( Peruraria lobata), is a specific inhibitor of ALDH2 and suppresses ethanol consumption. Daidzin is the active principle in a herbal remedy for "alcohol addiction" and provides a lead for the design of improved ALDH2. The structure of daidzin/ALDH2 in complex at 2.4 A resolution shows the isoflavone moiety of daidzin binding close to the aldehyde substrate-binding site in a hydrophobic cleft and the glucosyl function binding to a hydrophobic patch immediately outside the isoflavone-binding pocket. These observations provide an explanation for both the specificity and affinity of daidzin (IC50 =80 nM) and the affinity of analogues with different substituents at the glucosyl position.

PubMed: 18613661
DOI: 10.1021/JM800488J

実験手法

X-RAY DIFFRACTION (2.4 Å)