Crystal structure of human mitochondrial acyl-CoA thioesterase (ACOT2).
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.
Mandel
Corey R
CR
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Tweel
Benjamin
B
Tong
Liang
L
D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000737:chemistry; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006639:Histidine / Q000737:chemistry; D006801:Humans; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012694:Serine / Q000737:chemistry; D013869:Thiolester Hydrolases / Q000737:chemistry*
D001224:Aspartic Acid; D012694:Serine; D006639:Histidine; D013869:Thiolester Hydrolases; C413373:ACOT2 protein, human