2v1o
From Proteopedia
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==Overview== | ==Overview== | ||
| - | 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, ... | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 2V1O is a | + | 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]. |
==Reference== | ==Reference== | ||
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[[Category: serine esterase]] | [[Category: serine esterase]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:06:27 2007'' |
Revision as of 12:01, 5 November 2007
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CRYSTAL STRUCTURE OF N-TERMINAL DOMAIN OF ACYL-COA THIOESTERASE 7
Overview
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.
About this Structure
2V1O is a Single protein structure of sequence from Mus musculus with COA as ligand. Structure known Active Site: AC1. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Mon Nov 5 14:06:27 2007
Categories: Mus musculus | Single protein | Forwood, J.K. | Guncar, G. | Huber, T. | Hume, D.A. | Kellie, S. | Kobe, B. | Marfori, M. | Martin, J.L. | Meng, W.N. | Mouradov, D. | Robinson, J. | Thakur, A.S. | COA | Acot7 | Acyl-coa thioesterase 7 | Alternative splicing | Domain duplication | Hotdog domain | Hydrolase | Macrophage | Protein structure | Serine esterase
