6g5j: Difference between revisions
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==Secreted phospholipase A2 type X in complex with ligand== | |||
<StructureSection load='6g5j' size='340' side='right' caption='[[6g5j]], [[Resolution|resolution]] 1.85Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6g5j]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G5J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G5J FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EM8:(3~{R})-3-[3-[2-aminocarbonyl-6-(trifluoromethyloxy)indol-1-yl]phenyl]butanoic+acid'>EM8</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></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> | |||
<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=6g5j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g5j OCA], [http://pdbe.org/6g5j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g5j RCSB], [http://www.ebi.ac.uk/pdbsum/6g5j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g5j ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://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. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A lead generation campaign identified indole-based sPLA2-X inhibitors with a promising selectivity profile against other sPLA2 isoforms. Further optimization of sPLA2 selectivity and metabolic stability resulted in the design of (-)-17, a novel, potent, and selective sPLA2-X inhibitor with an exquisite pharmacokinetic profile characterized by high absorption and low clearance, and low toxicological risk. Compound (-)-17 was tested in an ApoE(-/-) murine model of atherosclerosis to evaluate the effect of reversible, pharmacological sPLA2-X inhibition on atherosclerosis development. Despite being well tolerated and achieving adequate systemic exposure of mechanistic relevance, (-)-17 did not significantly affect circulating lipid and lipoprotein biomarkers and had no effect on coronary function or histological markers of atherosclerosis. | |||
Design of Selective sPLA2-X Inhibitor (-)-2-{2-[Carbamoyl-6-(trifluoromethoxy)-1H-indol-1-yl]pyridine-2-yl}propanoic Acid.,Giordanetto F, Knerr L, Nordberg P, Pettersen D, Selmi N, Beisel HG, de la Motte H, Mansson A, Dahlstrom M, Broddefalk J, Saarinen G, Klingegard F, Hurt-Camejo E, Rosengren B, Wikstrom J, Wagberg M, Brengdahl J, Rohman M, Sandmark J, Akerud T, Roth RG, Jansen F, Ahlqvist M ACS Med Chem Lett. 2018 Jun 23;9(7):600-605. doi: 10.1021/acsmedchemlett.7b00507., eCollection 2018 Jul 12. PMID:30034586<ref>PMID:30034586</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6g5j" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Oster, L]] | [[Category: Oster, L]] | ||
[[Category: Sandmark, J]] | [[Category: Sandmark, J]] | ||
[[Category: Hydrolase]] | |||
[[Category: Secretory phospholipase a2 type x spla2x spla2-x phospholipase enzyme inhibitor complex]] | |||
Revision as of 10:12, 5 September 2018
Secreted phospholipase A2 type X in complex with ligand
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