3INJ

Human Mitochondrial Aldehyde Dehydrogenase complexed with agonist Alda-1

Summary for 3INJ

• Entry DOI: 10.2210/pdb3inj/pdb
• Related: 3INL
• Descriptor: Aldehyde dehydrogenase, mitochondrial, SODIUM ION, 1,2-ETHANEDIOL, ... (6 entities in total)
• Functional Keywords: oxidoreductase, aldh, e487k, rossmann fold, alda-1, activator, mitochondrion, nad, transit peptide
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion matrix: P05091
• Total number of polymer chains: 8
• Total formula weight: 440298.94

Authors

Perez-Miller, S.,Hurley, T.D. (deposition date: 2009-08-12, release date: 2010-01-12, Last modification date: 2024-11-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.688 Å)