|3inl, resolution 1.86Å ()|
|Gene:||ALDH2, ALDM (Homo sapiens)|
Human Mitochondrial Aldehyde Dehydrogenase Asian Variant, ALDH2*2, complexed with agonist Alda-1
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.
Alda-1 is an agonist and chemical chaperone for the common human aldehyde dehydrogenase 2 variant., Perez-Miller S, Younus H, Vanam R, Chen CH, Mochly-Rosen D, Hurley TD, Nat Struct Mol Biol. 2010 Feb;17(2):159-64. Epub 2010 Jan 10. PMID:20062057
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
- Perez-Miller S, Younus H, Vanam R, Chen CH, Mochly-Rosen D, Hurley TD. Alda-1 is an agonist and chemical chaperone for the common human aldehyde dehydrogenase 2 variant. Nat Struct Mol Biol. 2010 Feb;17(2):159-64. Epub 2010 Jan 10. PMID:20062057 doi:10.1038/nsmb.1737
- Chen CH, Budas GR, Churchill EN, Disatnik MH, Hurley TD, Mochly-Rosen D. Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. Science. 2008 Sep 12;321(5895):1493-5. PMID:18787169 doi:321/5895/1493
- Halioua B. The participation of Hans Hinselmann in medical experiments at Auschwitz. J Low Genit Tract Dis. 2010 Jan;14(1):1-4. PMID:20040829 doi:10.1097/LGT.0b013e3181af30ef