Identification of PTE2, a human peroxisomal long-chain acyl-CoA thioesterase.
Computer-based approaches identified PTE2 as a candidate human peroxisomal acyl-CoA thioesterase gene. The PTE2 gene product is highly similar to the rat cytosolic and mitochondrial thioesterases, CTE1 and MTE1, respectively, and terminates in a tripeptide sequence, serine-lysine-valine(COOH), that resembles the consensus sequence for type-1 peroxisomal targeting signals. PTE2 was targeted to peroxisomes and recombinant PTE2 showed intrinsic acyl-CoA thioesterase activity with a pH optimum of 8.5. A comparison of PTE2 and PTE1 thioesterase activities across multiple acyl-CoA substrates indicated that while PTE1 was most active on medium-chain acyl-CoAs, with little activity on long-chain acyl-CoAs, PTE2 displayed high activity on medium- and long-chain acyl-CoAs. The identification of PTE2 therefore offers an explanation for the observed long-chain acyl-CoA thioesterase activity of mammalian peroxisomes.
Jones
J M
JM
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA.
Gould
S J
SJ
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D016208:Databases, Factual; D005455:Fluorescent Antibody Technique; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008928:Mitochondria / Q000201:enzymology; D008969:Molecular Sequence Data; D005810:Multigene Family; D020675:Peroxisomes / Q000201:enzymology* / Q000378:metabolism; D010802:Phylogeny; D021382:Protein Sorting Signals; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D013379:Substrate Specificity; D013869:Thiolester Hydrolases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection
D000214:Acyl Coenzyme A; D021382:Protein Sorting Signals; D011994:Recombinant Proteins; D013869:Thiolester Hydrolases; C413373:ACOT2 protein, human