Crystal structure of human mitochondrial acyl-CoA thioesterase (ACOT2)

Biochem Biophys Res Commun. 2009 Aug 7;385(4):630-3. doi: 10.1016/j.bbrc.2009.05.122. Epub 2009 Jun 2.


Acyl-CoA thioesterases (ACOTs) catalyze the hydrolysis of CoA esters to free CoA and carboxylic acids and have important functions in lipid metabolism and other cellular processes. Type I ACOTs are found only in animals and contain an alpha/beta hydrolase domain, through currently no structural information is available on any of these enzymes. We report here the crystal structure at 2.1A resolution of human mitochondrial ACOT2, a type I enzyme. The structure contains two domains, N and C domains. The C domain has the alpha/beta hydrolase fold, with the catalytic triad Ser294-His422-Asp388. The N domain contains a seven-stranded beta-sandwich, which has some distant structural homologs in other proteins. The active site is located in a large pocket at the interface between the two domains. The structural information has significant relevance for other type I ACOTs and related enzymes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Aspartic Acid / chemistry
  • Catalytic Domain
  • Crystallography, X-Ray
  • Histidine / chemistry
  • Humans
  • Mitochondria / enzymology*
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Serine / chemistry
  • Thiolester Hydrolases / chemistry*


  • Aspartic Acid
  • Serine
  • Histidine
  • Thiolester Hydrolases
  • ACOT2 protein, human