5ixc: Difference between revisions
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==Human GIVD cytosolic phospholipase A2 in complex with Methyl gamma-Linolenyl Fluorophosphonate== | |||
<StructureSection load='5ixc' size='340' side='right'caption='[[5ixc]], [[Resolution|resolution]] 2.65Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5ixc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IXC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IXC FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.65Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7FA:METHYL+(R)-(6Z,9Z,12Z)-OCTADECA-6,9,12-TRIEN-1-YLPHOSPHONOFLUORIDATE'>7FA</scene>, <scene name='pdbligand=BA:BARIUM+ION'>BA</scene></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=5ixc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ixc OCA], [https://pdbe.org/5ixc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ixc RCSB], [https://www.ebi.ac.uk/pdbsum/5ixc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ixc ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PA24D_HUMAN PA24D_HUMAN] Calcium-dependent phospholipase A2 that selectively hydrolyzes glycerophospholipids in the sn-2 position. Not arachidonic acid-specific but has linoleic acid-specific activity. May play a role in inflammation in psoriatic lesions.<ref>PMID:14709560</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Cytosolic phospholipases A2 (cPLA2s) consist of a family of calcium-sensitive enzymes that function to generate lipid second messengers through hydrolysis of membrane-associated glycerophospholipids. The GIVD cPLA2 (cPLA2delta) is a potential drug target for developing a selective therapeutic agent for the treatment of psoriasis. Here, we present two X-ray structures of human cPLA2delta, capturing an apo state, and in complex with a substrate-like inhibitor. Comparison of the apo and inhibitor-bound structures reveals conformational changes in a flexible cap that allows the substrate to access the relatively buried active site, providing new insight into the mechanism for substrate recognition. The cPLA2delta structure reveals an unexpected second C2 domain that was previously unrecognized from sequence alignments, placing cPLA2delta into the class of membrane-associated proteins that contain a tandem pair of C2 domains. Furthermore, our structures elucidate novel inter-domain interactions and define three potential calcium-binding sites that are likely important for regulation and activation of enzymatic activity. These findings provide novel insights into the molecular mechanisms governing cPLA2's function in signal transduction. | |||
Structure of Human GIVD Cytosolic Phospholipase A2 Reveals Insights into Substrate Recognition.,Wang H, Klein MG, Snell G, Lane W, Zou H, Levin I, Li K, Sang BC J Mol Biol. 2016 Jul 3;428(13):2769-79. doi: 10.1016/j.jmb.2016.05.012. Epub 2016, May 21. PMID:27220631<ref>PMID:27220631</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Klein | <div class="pdbe-citations 5ixc" style="background-color:#fffaf0;"></div> | ||
[[Category: Wang | |||
==See Also== | |||
*[[Phospholipase A2 3D structures|Phospholipase A2 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Klein MG]] | |||
[[Category: Wang H]] | |||
Latest revision as of 13:36, 6 September 2023
Human GIVD cytosolic phospholipase A2 in complex with Methyl gamma-Linolenyl FluorophosphonateHuman GIVD cytosolic phospholipase A2 in complex with Methyl gamma-Linolenyl Fluorophosphonate
Structural highlights
FunctionPA24D_HUMAN Calcium-dependent phospholipase A2 that selectively hydrolyzes glycerophospholipids in the sn-2 position. Not arachidonic acid-specific but has linoleic acid-specific activity. May play a role in inflammation in psoriatic lesions.[1] Publication Abstract from PubMedCytosolic phospholipases A2 (cPLA2s) consist of a family of calcium-sensitive enzymes that function to generate lipid second messengers through hydrolysis of membrane-associated glycerophospholipids. The GIVD cPLA2 (cPLA2delta) is a potential drug target for developing a selective therapeutic agent for the treatment of psoriasis. Here, we present two X-ray structures of human cPLA2delta, capturing an apo state, and in complex with a substrate-like inhibitor. Comparison of the apo and inhibitor-bound structures reveals conformational changes in a flexible cap that allows the substrate to access the relatively buried active site, providing new insight into the mechanism for substrate recognition. The cPLA2delta structure reveals an unexpected second C2 domain that was previously unrecognized from sequence alignments, placing cPLA2delta into the class of membrane-associated proteins that contain a tandem pair of C2 domains. Furthermore, our structures elucidate novel inter-domain interactions and define three potential calcium-binding sites that are likely important for regulation and activation of enzymatic activity. These findings provide novel insights into the molecular mechanisms governing cPLA2's function in signal transduction. Structure of Human GIVD Cytosolic Phospholipase A2 Reveals Insights into Substrate Recognition.,Wang H, Klein MG, Snell G, Lane W, Zou H, Levin I, Li K, Sang BC J Mol Biol. 2016 Jul 3;428(13):2769-79. doi: 10.1016/j.jmb.2016.05.012. Epub 2016, May 21. PMID:27220631[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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