2vle is a 8 chain structure with sequence from Human. This structure supersedes the now removed PDB entry 1of7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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.
Structure of daidzin, a naturally occurring anti-alcohol-addiction agent, in complex with human mitochondrial aldehyde dehydrogenase.,Lowe ED, Gao GY, Johnson LN, Keung WM J Med Chem. 2008 Aug 14;51(15):4482-7. Epub 2008 Jul 10. PMID:18613661
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑ Lowe ED, Gao GY, Johnson LN, Keung WM. Structure of daidzin, a naturally occurring anti-alcohol-addiction agent, in complex with human mitochondrial aldehyde dehydrogenase. J Med Chem. 2008 Aug 14;51(15):4482-7. Epub 2008 Jul 10. PMID:18613661 doi:10.1021/jm800488j