View source for 6pwh


==Cystal structure of Myotoxin II from Bothrops moojeni co-crystallized with Varespladib (LY315920)==
<StructureSection load='6pwh' size='340' side='right'caption='[[6pwh]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6pwh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bothrops_moojeni Bothrops moojeni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PWH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PWH 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]] 1.749&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=VRD:2-[2-ethyl-3-oxamoyl-1-(phenylmethyl)indol-4-yl]oxyethanoic+acid'>VRD</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=6pwh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pwh OCA], [https://pdbe.org/6pwh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pwh RCSB], [https://www.ebi.ac.uk/pdbsum/6pwh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pwh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PA2H2_BOTMO PA2H2_BOTMO] Snake venom phospholipase A2 homolog that lack enzymatic activity. Displays myotoxin and edema-inducing activities.
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== Publication Abstract from PubMed ==
The World Health Organization recently listed snakebite envenoming as a Neglected Tropical Disease, proposing strategies to significantly reduce the global burden of this complex pathology by 2030. In this context, effective adjuvant treatments to complement conventional antivenom therapy based on inhibitory molecules for specific venom toxins have gained renewed interest. Varespladib (LY315920) is a synthetic molecule clinically tested to block inflammatory cascades of several diseases associated with elevated levels of secreted phospholipase A2 (sPLA2). Most recently, Varespladib was tested against several whole snake venoms and isolated PLA2 toxins, demonstrating potent inhibitory activity. Herein, we describe the first structural and functional study of the complex between Varespladib and a PLA2-like snake venom toxin (MjTX-II). In vitro and in vivo experiments showed this compound's capacity to inhibit the cytotoxic and myotoxic effects of MjTX-II from the medically important South American snake, Bothrops moojeni. Crystallographic and bioinformatics analyses revealed interactions of Varespladib with two specific regions of the toxin, suggesting inhibition occurs by physical blockage of its allosteric activation, preventing the alignment of its functional sites and, consequently, impairing its ability to disrupt membranes. Furthermore, based on the analysis of several crystallographic structures, a distinction between toxin activators and inhibitors is proposed.

Structural basis for phospholipase A2-like toxin inhibition by the synthetic compound Varespladib (LY315920).,Salvador GHM, Gomes AAS, Bryan-Quiros W, Fernandez J, Lewin MR, Gutierrez JM, Lomonte B, Fontes MRM Sci Rep. 2019 Nov 20;9(1):17203. doi: 10.1038/s41598-019-53755-5. PMID:31748642<ref>PMID:31748642</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 6pwh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Phospholipase A2 homolog|Phospholipase A2 homolog]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bothrops moojeni]]
[[Category: Large Structures]]
[[Category: Fontes MRM]]
[[Category: Salvador GHM]]