PDBsum entry 2vle

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chain
(+ 2 more) 494 a.a. *
DZN ×8
Waters ×1323
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: The structure of daidzin, a naturally occurring anti alcohol-addiction agent, in complex with human mitochondrial aldehyde dehydrogenase
Structure: Aldehyde dehydrogenase, mitochondrial. Chain: a, b, c, d, e, f, g, h. Fragment: residues 24-517. Synonym: aldh class 2, aldhi, aldh-e2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: liver. Expressed in: escherichia coli. Expression_system_taxid: 469008.
2.40Å     R-factor:   0.196     R-free:   0.249
Authors: E.D.Lowe,G.Y.Gao,L.N.Johnson,W.M.Keung
Key ref: E.D.Lowe et al. (2008). Structure of daidzin, a naturally occurring anti-alcohol-addiction agent, in complex with human mitochondrial aldehyde dehydrogenase. J Med Chem, 51, 4482-4487. PubMed id: 18613661 DOI: 10.1021/jm800488j
13-Jan-08     Release date:   19-Aug-08    
Supersedes: 1of7
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P05091  (ALDH2_HUMAN) -  Aldehyde dehydrogenase, mitochondrial
517 a.a.
494 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Aldehyde dehydrogenase (NAD(+)).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: An aldehyde + NAD+ + H2O = a carboxylate + NADH
+ NAD(+)
+ H(2)O
Bound ligand (Het Group name = DZN)
matches with 50.00% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular vesicular exosome   3 terms 
  Biological process     metabolic process   10 terms 
  Biochemical function     electron carrier activity     5 terms  


DOI no: 10.1021/jm800488j J Med Chem 51:4482-4487 (2008)
PubMed id: 18613661  
Structure of daidzin, a naturally occurring anti-alcohol-addiction agent, in complex with human mitochondrial aldehyde dehydrogenase.
E.D.Lowe, G.Y.Gao, L.N.Johnson, W.M.Keung.
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.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21318009 S.Manzo-Avalos, and A.Saavedra-Molina (2010).
Cellular and mitochondrial effects of alcohol consumption.
  Int J Environ Res Public Health, 7, 4281-4304.  
20062057 S.Perez-Miller, H.Younus, R.Vanam, C.H.Chen, D.Mochly-Rosen, and T.D.Hurley (2010).
Alda-1 is an agonist and chemical chaperone for the common human aldehyde dehydrogenase 2 variant.
  Nat Struct Mol Biol, 17, 159-164.
PDB codes: 3inj 3inl
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