PDBsum entry 3inl

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chain
(+ 2 more) 495 a.a. *
EDO ×31
BXB ×8
_NA ×8
Waters ×3408
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Human mitochondrial aldehyde dehydrogenase asian variant, al complexed with agonist alda-1
Structure: Aldehyde dehydrogenase, mitochondrial. Chain: a, b, c, d, e, f, g, h. Synonym: aldh class 2, aldhi, aldh-e2. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: aldh2, aldm. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.86Å     R-factor:   0.136     R-free:   0.168
Authors: S.Perez-Miller,T.D.Hurley
Key ref: S.Perez-Miller et al. (2010). Alda-1 is an agonist and chemical chaperone for the common human aldehyde dehydrogenase 2 variant. Nat Struct Mol Biol, 17, 159-164. PubMed id: 20062057
12-Aug-09     Release date:   12-Jan-10    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P05091  (ALDH2_HUMAN) -  Aldehyde dehydrogenase, mitochondrial
517 a.a.
495 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Aldehyde dehydrogenase (NAD(+)).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: An aldehyde + NAD+ + H2O = a carboxylate + NADH
Bound ligand (Het Group name = EDO)
matches with 40.00% similarity
+ NAD(+)
+ H(2)O
= carboxylate
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  


Nat Struct Mol Biol 17:159-164 (2010)
PubMed id: 20062057  
Alda-1 is an agonist and chemical chaperone for the common human aldehyde dehydrogenase 2 variant.
S.Perez-Miller, H.Younus, R.Vanam, C.H.Chen, D.Mochly-Rosen, T.D.Hurley.
In approximately one billion people, a point mutation inactivates a key detoxifying enzyme, aldehyde dehydrogenase (ALDH2). This mitochondrial enzyme metabolizes toxic biogenic and environmental aldehydes, including the endogenously produced 4-hydroxynonenal (4HNE) and the environmental pollutant acrolein, and also bioactivates nitroglycerin. ALDH2 is best known, however, for its role in ethanol metabolism. The accumulation of acetaldehyde following the consumption of even a single alcoholic beverage leads to the Asian alcohol-induced flushing syndrome in ALDH2*2 homozygotes. The ALDH2*2 allele is semidominant, and heterozygotic individuals show a similar but less severe phenotype. We recently identified a small molecule, Alda-1, that activates wild-type ALDH2 and restores near-wild-type activity to ALDH2*2. The structures of Alda-1 bound to ALDH2 and ALDH2*2 reveal how Alda-1 activates the wild-type enzyme and how it restores the activity of ALDH2*2 by acting as a structural chaperone.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20558439 C.H.Chen, L.Sun, and D.Mochly-Rosen (2010).
Mitochondrial aldehyde dehydrogenase and cardiac diseases.
  Cardiovasc Res, 88, 51-57.  
20716831 M.Sano (2010).
Cardioprotection by hormetic responses to aldehyde.
  Circ J, 74, 1787-1793.  
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