spacer
spacer

PDBsum entry 3inj

Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
3inj
Jmol
Contents
Protein chain
(+ 2 more) 494 a.a. *
Ligands
EDO ×16
GAI ×9
BXB ×8
Metals
_NA ×8
Waters ×4009
* Residue conservation analysis
PDB id:
3inj
Name: Oxidoreductase
Title: Human mitochondrial aldehyde dehydrogenase complexed with ag alda-1
Structure: Aldehyde dehydrogenase, mitochondrial. Chain: a, b, c, d, e, f, g, h. Synonym: aldh class 2, aldhi, aldh-e2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: aldh2, aldm. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.69Å     R-factor:   0.180     R-free:   0.200
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
Date:
12-Aug-09     Release date:   12-Jan-10    
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
Bound ligand (Het Group name = EDO)
matches with 40.00% similarity
+ NAD(+)
+ H(2)O
= carboxylate
+ 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    
 
 
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.
 
  ABSTRACT  
 
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.  
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.