2q2b
From Proteopedia
(New page: 200px<br /><applet load="2q2b" size="450" color="white" frame="true" align="right" spinBox="true" caption="2q2b, resolution 2.50Å" /> '''Crystal structure of...) |
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| - | [[Image:2q2b.jpg|left|200px]]<br /><applet load="2q2b" size=" | + | [[Image:2q2b.jpg|left|200px]]<br /><applet load="2q2b" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2q2b, resolution 2.50Å" /> | caption="2q2b, resolution 2.50Å" /> | ||
'''Crystal structure of the C-terminal domain of mouse acyl-CoA thioesterase 7'''<br /> | '''Crystal structure of the C-terminal domain of mouse acyl-CoA thioesterase 7'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2Q2B is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [http://en.wikipedia.org/wiki/Palmitoyl-CoA_hydrolase Palmitoyl-CoA hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.2 3.1.2.2] Full crystallographic information is available from [http:// | + | 2Q2B is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [http://en.wikipedia.org/wiki/Palmitoyl-CoA_hydrolase Palmitoyl-CoA hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.2 3.1.2.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q2B OCA]. |
==Reference== | ==Reference== | ||
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[[Category: c-terminal domain]] | [[Category: c-terminal domain]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:32:38 2008'' |
Revision as of 12:32, 23 January 2008
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Crystal structure of the C-terminal domain of mouse 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
2Q2B is a Single protein structure of sequence from Mus musculus. Active as Palmitoyl-CoA hydrolase, with EC number 3.1.2.2 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
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