PDBsum entry 3sz9

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase/oxidoreductase inhibitor PDB id
Protein chain
(+ 2 more) 494 a.a.
GAI ×18
EDO ×21
I3E ×8
_NA ×8
Waters ×2597
PDB id:
Name: Oxidoreductase/oxidoreductase inhibitor
Title: Crystal structure of human aldh2 modified with the beta-elim product of aldi-3; 1-(4-ethylbenzene)prop-2-en-1-one
Structure: Aldehyde dehydrogenase, mitochondrial. Chain: a, b, c, d, e, f, g, h. Fragment: mature sequence, unp residues 18-517. Synonym: aldh class 2, aldh-e2, aldhi. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: aldh2, aldm. Expressed in: escherichia coli. Expression_system_taxid: 469008.
2.10Å     R-factor:   0.176     R-free:   0.226
Authors: S.Perez-Miller,T.D.Hurley
Key ref: M.Khanna et al. (2011). Discovery of a novel class of covalent inhibitor for aldehyde dehydrogenases. J Biol Chem, 286, 43486-43494. PubMed id: 22021038 DOI: 10.1074/jbc.M111.293597
18-Jul-11     Release date:   02-Nov-11    
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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
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  


DOI no: 10.1074/jbc.M111.293597 J Biol Chem 286:43486-43494 (2011)
PubMed id: 22021038  
Discovery of a novel class of covalent inhibitor for aldehyde dehydrogenases.
M.Khanna, C.H.Chen, A.Kimble-Hill, B.Parajuli, S.Perez-Miller, S.Baskaran, J.Kim, K.Dria, V.Vasiliou, D.Mochly-Rosen, T.D.Hurley.
Human aldehyde dehydrogenases (ALDHs) comprise a family of 17 homologous enzymes that metabolize different biogenic and exogenic aldehydes. To date, there are relatively few general ALDH inhibitors that can be used to probe the contribution of this class of enzymes to particular metabolic pathways. Here, we report the discovery of a general class of ALDH inhibitors with a common mechanism of action. The combined data from kinetic studies, mass spectrometric measurements, and crystallographic analyses demonstrate that these inhibitors undergo an enzyme-mediated β-elimination reaction generating a vinyl ketone intermediate that covalently modifies the active site cysteine residue present in these enzymes. The studies described here can provide the basis for rational approach to design ALDH isoenzyme-specific inhibitors as research tools and perhaps as drugs, to address diseases such as cancer where increased ALDH activity is associated with a cellular phenotype.