3INJ

Human Mitochondrial Aldehyde Dehydrogenase complexed with agonist Alda-1

3INJ の概要

• エントリーDOI: 10.2210/pdb3inj/pdb
• 関連するPDBエントリー: 3INL
• 分子名称: Aldehyde dehydrogenase, mitochondrial, SODIUM ION, 1,2-ETHANEDIOL, ... (6 entities in total)
• 機能のキーワード: oxidoreductase, aldh, e487k, rossmann fold, alda-1, activator, mitochondrion, nad, transit peptide
• 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: 440298.94

構造登録者

Perez-Miller, S.,Hurley, T.D. (登録日: 2009-08-12, 公開日: 2010-01-12, 最終更新日: 2024-11-06)

主引用文献

Perez-Miller, S.,Younus, H.,Vanam, R.,Chen, C.H.,Mochly-Rosen, D.,Hurley, T.D.
Alda-1 is an agonist and chemical chaperone for the common human aldehyde dehydrogenase 2 variant.
Nat.Struct.Mol.Biol., 17:159-164, 2010

PubMed Abstract: In approximately one billion people, a point mutation inactivates a key detoxifying enzyme, aldehyde dehydrogenase (ALDH2). This mitochondrial enzyme metabolizes toxic biogenic and environmental aldehydes, including the endogenously produced 4-hydroxynonenal (4HNE) and the environmental pollutant acrolein, and also bioactivates nitroglycerin. ALDH2 is best known, however, for its role in ethanol metabolism. The accumulation of acetaldehyde following the consumption of even a single alcoholic beverage leads to the Asian alcohol-induced flushing syndrome in ALDH2*2 homozygotes. The ALDH2*2 allele is semidominant, and heterozygotic individuals show a similar but less severe phenotype. We recently identified a small molecule, Alda-1, that activates wild-type ALDH2 and restores near-wild-type activity to ALDH2*2. The structures of Alda-1 bound to ALDH2 and ALDH2*2 reveal how Alda-1 activates the wild-type enzyme and how it restores the activity of ALDH2*2 by acting as a structural chaperone.

PubMed: 20062057
DOI: 10.1038/nsmb.1737

実験手法

X-RAY DIFFRACTION (1.688 Å)