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| {{STRUCTURE_2v1o| PDB=2v1o | SCENE= }} | | {{STRUCTURE_2v1o| PDB=2v1o | SCENE= }} |
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| '''CRYSTAL STRUCTURE OF N-TERMINAL DOMAIN OF ACYL-COA THIOESTERASE 7'''
| | ===CRYSTAL STRUCTURE OF N-TERMINAL DOMAIN OF ACYL-COA THIOESTERASE 7=== |
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| ==Overview==
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| Acyl-CoA thioesterases (Acots) catalyze the hydrolysis of fatty acyl-CoA to free fatty acid and CoA and thereby regulate lipid metabolism and cellular signaling. We present a comprehensive structural and functional characterization of mouse acyl-CoA thioesterase 7 (Acot7). Whereas prokaryotic homologues possess a single thioesterase domain, mammalian Acot7 contains a pair of domains in tandem. We determined the crystal structures of both the N- and C-terminal domains of the mouse enzyme, and inferred the structure of the full-length enzyme using a combination of chemical cross-linking, mass spectrometry, and molecular modeling. The quaternary arrangement in Acot7 features a trimer of hotdog fold dimers. Both domains of Acot7 are required for activity, but only one of two possible active sites in the dimer is functional. Asn-24 and Asp-213 (from N- and C-domains, respectively) were identified as the catalytic residues through site-directed mutagenesis. An enzyme with higher activity than wild-type Acot7 was obtained by mutating the residues in the nonfunctional active site. Recombinant Acot7 was shown to have the highest activity toward arachidonoyl-CoA, suggesting a function in eicosanoid metabolism. In line with the proposal, Acot7 was shown to be highly expressed in macrophages and up-regulated by lipopolysaccharide. Overexpression of Acot7 in a macrophage cell line modified the production of prostaglandins D2 and E2. Together, the results link the molecular and cellular functions of Acot7 and identify the enzyme as a candidate drug target in inflammatory disease.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17563367}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17563367 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17563367}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Protein structure]] | | [[Category: Protein structure]] |
| [[Category: Serine esterase]] | | [[Category: Serine esterase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 18:02:59 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 12:33:03 2008'' |
