PDBsum entry 4fqf

Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chain
488 a.a.
2NO ×4
NAD ×4
URE ×6
_NA ×4
_MG ×4
Waters ×889
PDB id:
Name: Oxidoreductase
Title: Crystal structure of a thionitrate intermediate of human ald dehydrogenase-2
Structure: Aldehyde dehydrogenase, mitochondrial. Chain: a, b, c, d. Fragment: 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: 562
2.28Å     R-factor:   0.172     R-free:   0.209
Authors: B.S.Lang,K.Gruber
Key ref: B.S.Lang et al. (2012). Vascular bioactivation of nitroglycerin by aldehyde dehydrogenase-2: reaction intermediates revealed by crystallography and mass spectrometry. J Biol Chem, 287, 38124-38134. PubMed id: 22988236 DOI: 10.1074/jbc.M112.371716
25-Jun-12     Release date:   26-Sep-12    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P05091  (ALDH2_HUMAN) -  Aldehyde dehydrogenase, mitochondrial
517 a.a.
488 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 = URE)
matches with 40.00% similarity
Bound ligand (Het Group name = NAD)
corresponds exactly
+ 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.M112.371716 J Biol Chem 287:38124-38134 (2012)
PubMed id: 22988236  
Vascular bioactivation of nitroglycerin by aldehyde dehydrogenase-2: reaction intermediates revealed by crystallography and mass spectrometry.
B.S.Lang, A.C.Gorren, G.Oberdorfer, M.V.Wenzl, C.M.Furdui, L.B.Poole, B.Mayer, K.Gruber.
Aldehyde dehydrogenase-2 (ALDH2) catalyzes the bioactivation of nitroglycerin (glyceryl trinitrate, GTN) in blood vessels, resulting in vasodilation by nitric oxide (NO) or a related species. Because the mechanism of this reaction is still unclear we determined the three-dimensional structures of wild-type (WT) ALDH2 and of a triple mutant of the protein that exhibits low denitration activity (E268Q/C301S/C303S) in complex with GTN. The structure of the triple mutant showed that GTN binds to the active site via polar contacts to the oxyanion hole and to residues 268 and 301 as well as by van der Waals interactions to hydrophobic residues of the catalytic pocket. The structure of the GTN-soaked wild-type protein revealed a thionitrate adduct to Cys-302 as the first reaction intermediate, which was also found by mass spectrometry (MS) experiments. In addition, the MS data identified sulfinic acid as the irreversibly inactivated enzyme species. Assuming that the structures of the triple mutant and wild-type ALDH2 reflect binding of GTN to the catalytic site and the first reaction step, respectively, superposition of the two structures indicates that denitration of GTN is initiated by nucleophilic attack of Cys-302 at one of the terminal nitrate groups, resulting in formation of the observed thionitrate intermediate and release of 1,2-glyceryl dinitrate. Our results shed light on the molecular mechanism of the GTN denitration reaction and provide useful information on the structural requirements for high affinity binding of organic nitrates to the catalytic site of ALDH2.