3SZB

Crystal structure of human ALDH3A1 modified with the beta-elimination product of Aldi-1; 1-phenyl- 2-propen-1-one

3SZB の概要

• エントリーDOI: 10.2210/pdb3szb/pdb
• 関連するPDBエントリー: 3SZ9 3SZA
• 分子名称: Aldehyde dehydrogenase, POTASSIUM ION, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: aldh, aldi-1, inhibitor, rossmann fold, covalent adduct, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : P30838
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 105034.31

構造登録者

Khanna, M.,Hurley, T.D. (登録日: 2011-07-18, 公開日: 2011-11-02, 最終更新日: 2024-11-20)

主引用文献

Khanna, M.,Chen, C.H.,Kimble-Hill, A.,Parajuli, B.,Perez-Miller, S.,Baskaran, S.,Kim, J.,Dria, K.,Vasiliou, V.,Mochly-Rosen, D.,Hurley, T.D.
Discovery of a novel class of covalent inhibitor for aldehyde dehydrogenases.
J.Biol.Chem., 286:43486-43494, 2011

PubMed Abstract: Human aldehyde dehydrogenases (ALDHs) comprise a family of 17 homologous enzymes that metabolize different biogenic and exogenic aldehydes. To date, there are relatively few general ALDH inhibitors that can be used to probe the contribution of this class of enzymes to particular metabolic pathways. Here, we report the discovery of a general class of ALDH inhibitors with a common mechanism of action. The combined data from kinetic studies, mass spectrometric measurements, and crystallographic analyses demonstrate that these inhibitors undergo an enzyme-mediated β-elimination reaction generating a vinyl ketone intermediate that covalently modifies the active site cysteine residue present in these enzymes. The studies described here can provide the basis for rational approach to design ALDH isoenzyme-specific inhibitors as research tools and perhaps as drugs, to address diseases such as cancer where increased ALDH activity is associated with a cellular phenotype.

PubMed: 22021038
DOI: 10.1074/jbc.M111.293597

実験手法

X-RAY DIFFRACTION (1.51 Å)