2VLE

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.196 

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This is version 1.3 of the entry. See complete history


Literature

Structure of Daidzin, a Naturally Occurring Anti-Alcohol-Addiction Agent, in Complex with Human Mitochondrial Aldehyde Dehydrogenase.

Lowe, E.D.Gao, G.Y.Johnson, L.N.Keung, W.M.

(2008) J Med Chem 51: 4482

  • DOI: https://doi.org/10.1021/jm800488j
  • Primary Citation of Related Structures:  
    2VLE

  • 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.


  • Organizational Affiliation

    Laboratory of Molecular Biophysics, University of Oxford, Rex Richards Building, Oxford OX1 3QU, UK. edl@biop.ox.ac.uk


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ALDEHYDE DEHYDROGENASE, MITOCHONDRIAL
A, B, C, D, E
A, B, C, D, E, F, G, H
494Homo sapiensMutation(s): 0 
EC: 1.2.1.3
UniProt & NIH Common Fund Data Resources
Find proteins for P05091 (Homo sapiens)
Explore P05091 
Go to UniProtKB:  P05091
PHAROS:  P05091
GTEx:  ENSG00000111275 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP05091
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.196 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 142.77α = 90
b = 150.99β = 90
c = 176.99γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
MOSFLMdata reduction
SCALAdata scaling
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-08-19
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-12-13
    Changes: Data collection, Database references, Other, Refinement description