2v1o

Crystal structure of N-terminal domain of acyl-CoA thioesterase 7

spinqualitylabelsall models 2v1o, resolution 1.78Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2v1o is a 6 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.78Å Ligands: COA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BACH_MOUSE Acyl-CoA thioesterases are a group of enzymes that catalyze the hydrolysis of acyl-CoAs to the free fatty acid and coenzyme A (CoASH), providing the potential to regulate intracellular levels of acyl-CoAs, free fatty acids and CoASH. May play an important physiological function in brain. May play a regulatory role by modulating the cellular levels of fatty acyl-CoA ligands for certain transcription factors as well as the substrates for fatty acid metabolizing enzymes, contributing to lipid homeostasis. Has broad specificity, active towards fatty acyl-CoAs with chain-lengths of C8-C18. Has a maximal activity toward palmitoyl-CoA. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. Structural basis for recruitment of tandem hotdog domains in acyl-CoA thioesterase 7 and its role in inflammation.,Forwood JK, Thakur AS, Guncar G, Marfori M, Mouradov D, Meng W, Robinson J, Huber T, Kellie S, Martin JL, Hume DA, Kobe B Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10382-7. Epub 2007 Jun 11. PMID:17563367 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thioesterase 3D structures

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