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PDBsum entry 2vle

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
2vle
Jmol
Contents
Protein chain
(+ 2 more) 494 a.a. *
Ligands
DZN ×8
Waters ×1323
* Residue conservation analysis
PDB id:
2vle
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.
Resolution:
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
Date:
13-Jan-08     Release date:   19-Aug-08    
Supersedes: 1of7
PROCHECK
Go to PROCHECK summary
 Headers
 References

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

 Enzyme reactions 
   Enzyme class: E.C.1.2.1.3  - Aldehyde dehydrogenase (NAD(+)).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: An aldehyde + NAD+ + H2O = a carboxylate + NADH
aldehyde
+ NAD(+)
+ H(2)O
=
carboxylate
Bound ligand (Het Group name = DZN)
matches with 50.00% similarity
+ NADH
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  

 

 
    reference    
 
 
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.
 
  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.
 

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
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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