View source for 5g3m


==Discovery of a novel secreted phospholipase A2 (sPLA2) inhibitor.==
<StructureSection load='5g3m' size='340' side='right'caption='[[5g3m]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5g3m]] 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=5G3M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5G3M 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]] 1.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9JH:4-BENZYLBENZAMIDE'>9JH</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=5g3m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g3m OCA], [https://pdbe.org/5g3m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5g3m RCSB], [https://www.ebi.ac.uk/pdbsum/5g3m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5g3m ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PA2GX_HUMAN PA2GX_HUMAN] PA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Has a powerful potency for releasing arachidonic acid from cell membrane phospholipids. Prefers phosphatidylethanolamine and phosphatidylcholine liposomes to those of phosphatidylserine.
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== Publication Abstract from PubMed ==
Expedited structure-based optimization of the initial fragment hit 1 led to the design of (R)-7 (AZD2716) a novel, potent secreted phospholipase A2 (sPLA2) inhibitor with excellent preclinical pharmacokinetic properties across species, clear in vivo efficacy, and minimized safety risk. Based on accumulated profiling data, (R)-7 was selected as a clinical candidate for the treatment of coronary artery disease.

Discovery of AZD2716: A Novel Secreted Phospholipase A2 (sPLA2) Inhibitor for the Treatment of Coronary Artery Disease.,Giordanetto F, Pettersen D, Starke I, Nordberg P, Dahlstrom M, Knerr L, Selmi N, Rosengren B, Larsson LO, Sandmark J, Castaldo M, Dekker N, Karlsson U, Hurt-Camejo E ACS Med Chem Lett. 2016 Aug 9;7(10):884-889. eCollection 2016 Oct 13. PMID:27774123<ref>PMID:27774123</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5g3m" style="background-color:#fffaf0;"></div>

==See Also==
*[[Phospholipase A2 3D structures|Phospholipase A2 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bodin C]]
[[Category: Hallberg K]]
[[Category: Sandmark J]]