2VLE

The structure of daidzin, a naturally occurring anti alcohol- addiction agent, in complex with human mitochondrial aldehyde dehydrogenase

Replaces:  1OF7

Summary for 2VLE

• Entry DOI: 10.2210/pdb2vle/pdb
• Related: 1CW3 1NZW 1NZX 1NZZ 1O00 1O01 1O02 1O04 1O05 1ZUM
• Descriptor: ALDEHYDE DEHYDROGENASE, MITOCHONDRIAL, DAIDZIN (3 entities in total)
• Functional Keywords: transit peptide, aldehyde dehydrogenase, nad, daidzin, acetylation, polymorphism, mitochondrion, alcohol abuse, oxidoreductase
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Mitochondrion matrix: P05091
• Total number of polymer chains: 8
• Total formula weight: 435091.74

Authors

Lowe, E.D.,Gao, G.Y.,Johnson, L.N.,Keung, W.M. (deposition date: 2008-01-13, release date: 2008-08-19, Last modification date: 2023-12-13)

Primary citation

Lowe, E.D.,Gao, G.Y.,Johnson, L.N.,Keung, W.M.
Structure of Daidzin, a Naturally Occurring Anti-Alcohol-Addiction Agent, in Complex with Human Mitochondrial Aldehyde Dehydrogenase.
J.Med.Chem., 51:4482-, 2008

PubMed Abstract: 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.

PubMed: 18613661
DOI: 10.1021/JM800488J

Experimental method

X-RAY DIFFRACTION (2.4 Å)