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

Publication Type:

Journal Article

Authors:

Mandel, Corey R; Tweel, Benjamin; Tong, Liang

Source:

Biochem Biophys Res Commun, Volume 385, Issue 4, p.630-3 (2009)

Keywords:

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

Abstract:

<p>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.</p>