6aun: Difference between revisions

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 <StructureSection load='6aun' size='340' side='right'caption='[[6aun]], [[Resolution|resolution]] 3.95&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6aun]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Cho_cell_lines Cho cell lines]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AUN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AUN FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6aun]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cricetulus_griseus Cricetulus griseus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AUN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AUN FirstGlance]. <br>
-</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phospholipase_A(2) Phospholipase A(2)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.4 3.1.1.4] </span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.951&#8491;</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6aun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aun OCA], [http://pdbe.org/6aun PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aun RCSB], [http://www.ebi.ac.uk/pdbsum/6aun PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aun ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6aun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aun OCA], [https://pdbe.org/6aun PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6aun RCSB], [https://www.ebi.ac.uk/pdbsum/6aun PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6aun ProSAT]</span></td></tr>
 </table>
-<div style="background-color:#fffaf0;">
+== Function ==
-== Publication Abstract from PubMed ==
+[https://www.uniprot.org/uniprot/PLPL9_CRIGR PLPL9_CRIGR] Calcium-independent phospholipase involved in phospholipid remodeling with implications in cellular membrane homeostasis, mitochondrial integrity and signal transduction. Hydrolyzes the ester bond of the fatty acyl group attached at sn-1 or sn-2 position of phospholipids (phospholipase A1 and A2 activity respectively), producing lysophospholipids that are used in deacylation-reacylation cycles. Hydrolyzes both saturated and unsaturated long fatty acyl chains in various glycerophospholipid classes such as phosphatidylcholines, phosphatidylethanolamines and phosphatidates, with a preference for hydrolysis at sn-2 position (PubMed:9079687, PubMed:15908428). Can further hydrolyze lysophospholipids carrying saturated fatty acyl chains (lysophospholipase activity) (PubMed:9079687). Upon oxidative stress, contributes to remodeling of mitochondrial phospholipids in pancreatic beta cells, in a repair mechanism to reduce oxidized lipid content (By similarity). Preferentially hydrolyzes oxidized polyunsaturated fatty acyl chains from cardiolipins, yielding monolysocardiolipins that can be reacylated with unoxidized fatty acyls to regenerate native cardiolipin species. Hydrolyzes oxidized glycerophosphoethanolamines present in pancreatic islets, releasing oxidized polyunsaturated fatty acids such as hydroxyeicosatetraenoates (HETEs) (By similarity). Has thioesterase activity toward fatty-acyl CoA releasing CoA-SH known to facilitate fatty acid transport and beta-oxidation in mitochondria particularly in skeletal muscle (By similarity). Plays a role in regulation of membrane dynamics and homeostasis. Selectively hydrolyzes sn-2 arachidonoyl group in plasmalogen phospholipids, structural components of lipid rafts and myelin (PubMed:9079687). Regulates F-actin polymerization at the pseudopods, which is required for both speed and directionality of MCP1/CCL2-induced monocyte chemotaxis (By similarity). Targets membrane phospholipids to produce potent lipid signaling messengers. Generates lysophosphatidate (LPA, 1-acyl-glycerol-3-phosphate), which acts via G-protein receptors in various cell types (PubMed:9079687). Has phospholipase A2 activity toward platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), likely playing a role in inactivation of this potent pro-inflammatory signaling lipid (PubMed:9079687). In response to glucose, amplifies calcium influx in pancreatic beta cells to promote INS secretion (By similarity).[UniProtKB:O60733][UniProtKB:P97570][UniProtKB:P97819]<ref>PMID:15908428</ref> <ref>PMID:9079687</ref>
-Calcium-independent phospholipase A2beta (iPLA2beta) regulates important physiological processes including inflammation, calcium homeostasis and apoptosis. It is genetically linked to neurodegenerative disorders including Parkinson's disease. Despite its known enzymatic activity, the mechanisms underlying iPLA2beta-induced pathologic phenotypes remain poorly understood. Here, we present a crystal structure of iPLA2beta that significantly revises existing mechanistic models. The catalytic domains form a tight dimer. They are surrounded by ankyrin repeat domains that adopt an outwardly flared orientation, poised to interact with membrane proteins. The closely integrated active sites are positioned for cooperative activation and internal transacylation. The structure and additional solution studies suggest that both catalytic domains can be bound and allosterically inhibited by a single calmodulin. These features suggest mechanisms of iPLA2beta cellular localization and activity regulation, providing a basis for inhibitor development. Furthermore, the structure provides a framework to investigate the role of neurodegenerative mutations and the function of iPLA2beta in the brain.
-The structure of iPLA2beta reveals dimeric active sites and suggests mechanisms of regulation and localization.,Malley KR, Koroleva O, Miller I, Sanishvili R, Jenkins CM, Gross RW, Korolev S Nat Commun. 2018 Feb 22;9(1):765. doi: 10.1038/s41467-018-03193-0. PMID:29472584<ref>PMID:29472584</ref>
+==See Also==
+*[[Phospholipase A2 3D structures|Phospholipase A2 3D structures]]
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 6aun" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Cho cell lines]]
+[[Category: Cricetulus griseus]]
 [[Category: Large Structures]]
-[[Category: Gross, R W]]
+[[Category: Gross RW]]
-[[Category: Jenkins, C M]]
+[[Category: Jenkins CM]]
-[[Category: Korolev, S]]
+[[Category: Korolev S]]
-[[Category: Koroleva, O]]
+[[Category: Koroleva O]]
-[[Category: Malley, K]]
+[[Category: Malley K]]
-[[Category: Miller, I]]
+[[Category: Miller I]]
-[[Category: Sanishvili, R]]
+[[Category: Sanishvili R]]
-[[Category: Atp binding]]
-[[Category: Calcium-independent]]
-[[Category: Calmodulin binding]]
-[[Category: Hydrolase]]
-[[Category: Ipla2beta]]
-[[Category: Phospholipase]]
-[[Category: Pla2g6]]
-[[Category: Pnpla9]]