1wab: Difference between revisions
New page: left|200px<br /><applet load="1wab" size="450" color="white" frame="true" align="right" spinBox="true" caption="1wab, resolution 1.7Å" /> '''PLATELET-ACTIVATING F... |
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[[Image:1wab.gif|left|200px]]<br /><applet load="1wab" size=" | [[Image:1wab.gif|left|200px]]<br /><applet load="1wab" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1wab, resolution 1.7Å" /> | caption="1wab, resolution 1.7Å" /> | ||
'''PLATELET-ACTIVATING FACTOR ACETYLHYDROLASE'''<br /> | '''PLATELET-ACTIVATING FACTOR ACETYLHYDROLASE'''<br /> | ||
==Overview== | ==Overview== | ||
The platelet-activating factor PAF | The platelet-activating factor PAF (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent lipid first messenger active in general cell activation, fertilization, inflammatory and allergic reactions, asthma, HIV pathogenesis, carcinogenesis, and apoptosis. There is substantial evidence that PAF is involved in intracellular signalling, but the pathways are poorly understood. Inactivation of PAF is carried out by specific intra- and extracellular acetylhydrolases (PAF-AHs), a subfamily of phospholipases A2 that remove the sn-2 acetyl group. Mammalian brain contains at least three intracellular isoforms, of which PAF-AH(Ib) is the best characterized. This isoform contains a heterodimer of two homologous catalytic subunits alpha1 and alpha2, each of relative molecular mass 26K, and a non-catalytic 45K beta-subunit, a homologue of the beta-subunit of trimeric G proteins. We now report the crystal structure of the bovine alpha1 subunit of PAF-AH(Ib) at 1.7 A resolution in complex with a reaction product, acetate. The tertiary fold of this protein is closely reminiscent of that found in p21(ras) and other GTPases. The active site is made up of a trypsin-like triad of Ser 47, His 195 and Asp 192. Thus, the intact PAF-AH(Ib) molecule is an unusual G-protein-like (alpha1/alpha2)beta trimer. | ||
==About this Structure== | ==About this Structure== | ||
1WAB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with ACT as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/1-alkyl-2-acetylglycerophosphocholine_esterase 1-alkyl-2-acetylglycerophosphocholine esterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.47 3.1.1.47] Full crystallographic information is available from [http:// | 1WAB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=ACT:'>ACT</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/1-alkyl-2-acetylglycerophosphocholine_esterase 1-alkyl-2-acetylglycerophosphocholine esterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.47 3.1.1.47] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WAB OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Dauter, Z.]] | [[Category: Dauter, Z.]] | ||
[[Category: Derewenda, U.]] | [[Category: Derewenda, U.]] | ||
[[Category: Derewenda, Z | [[Category: Derewenda, Z S.]] | ||
[[Category: Hattori, M.]] | [[Category: Hattori, M.]] | ||
[[Category: Ho, Y | [[Category: Ho, Y S.]] | ||
[[Category: Inoue, K.]] | [[Category: Inoue, K.]] | ||
[[Category: Serre, L.]] | [[Category: Serre, L.]] | ||
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[[Category: platelet factor]] | [[Category: platelet factor]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:42:09 2008'' | ||
Revision as of 16:42, 21 February 2008
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PLATELET-ACTIVATING FACTOR ACETYLHYDROLASE
OverviewOverview
The platelet-activating factor PAF (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent lipid first messenger active in general cell activation, fertilization, inflammatory and allergic reactions, asthma, HIV pathogenesis, carcinogenesis, and apoptosis. There is substantial evidence that PAF is involved in intracellular signalling, but the pathways are poorly understood. Inactivation of PAF is carried out by specific intra- and extracellular acetylhydrolases (PAF-AHs), a subfamily of phospholipases A2 that remove the sn-2 acetyl group. Mammalian brain contains at least three intracellular isoforms, of which PAF-AH(Ib) is the best characterized. This isoform contains a heterodimer of two homologous catalytic subunits alpha1 and alpha2, each of relative molecular mass 26K, and a non-catalytic 45K beta-subunit, a homologue of the beta-subunit of trimeric G proteins. We now report the crystal structure of the bovine alpha1 subunit of PAF-AH(Ib) at 1.7 A resolution in complex with a reaction product, acetate. The tertiary fold of this protein is closely reminiscent of that found in p21(ras) and other GTPases. The active site is made up of a trypsin-like triad of Ser 47, His 195 and Asp 192. Thus, the intact PAF-AH(Ib) molecule is an unusual G-protein-like (alpha1/alpha2)beta trimer.
About this StructureAbout this Structure
1WAB is a Single protein structure of sequence from Bos taurus with as ligand. Active as 1-alkyl-2-acetylglycerophosphocholine esterase, with EC number 3.1.1.47 Full crystallographic information is available from OCA.
ReferenceReference
Brain acetylhydrolase that inactivates platelet-activating factor is a G-protein-like trimer., Ho YS, Swenson L, Derewenda U, Serre L, Wei Y, Dauter Z, Hattori M, Adachi T, Aoki J, Arai H, Inoue K, Derewenda ZS, Nature. 1997 Jan 2;385(6611):89-93. PMID:8985254
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