View source for 4uy1


==Novel pyrazole series of group X Secretory Phospholipase A2 (sPLA2-X) inhibitors==
<StructureSection load='4uy1' size='340' side='right'caption='[[4uy1]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4uy1]] 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=4UY1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UY1 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</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>, <scene name='pdbligand=TJM:5-(2,5-DIMETHYL-3-THIENYL)-1H-PYRAZOLE-3-CARBOXAMIDE'>TJM</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=4uy1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uy1 OCA], [https://pdbe.org/4uy1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uy1 RCSB], [https://www.ebi.ac.uk/pdbsum/4uy1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uy1 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 ==
The discovery of potent novel pyrazole containing group X secreted phospholipase A2 inhibitors via structure based virtual screening is reported. Docking was applied on a large set of in-house fragment collection and pharmacophore feature matching was used to filter docking poses. The selected virtual screening hits was run in NMR screening, a potent pyrazole containing fragment hit was identified and confirmed by its complex X-ray structure and the following biochemical assay result. Expansion on the fragment hit has led to further improvement of potency while maintaining high ligand efficiency, thus supporting the further development of this chemical series.

Discovery of a novel pyrazole series of group X secreted phospholipase A2 inhibitor (sPLAX) via fragment based virtual screening.,Chen H, Knerr L, Kerud T, Hallberg K, Oster L, Rohman M, Osterlund K, Beisel HG, Olsson T, Brengdhal J, Sandmark J, Bodin C Bioorg Med Chem Lett. 2014 Sep 30. pii: S0960-894X(14)01011-7. doi:, 10.1016/j.bmcl.2014.09.058. PMID:25316315<ref>PMID:25316315</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4uy1" 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: Chen H]]
[[Category: Hallberg K]]
[[Category: Oster L]]
[[Category: Sandmark J]]