2v1o: Difference between revisions

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.

2V1O is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with COA as [http://en.wikipedia.org/wiki/ligand ligand]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2V1O OCA].  

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