7lye - Revision history

OCA at 16:01, 18 October 2023

2023-10-18T16:01:18Z

←Older revision		Revision as of 16:01, 18 October 2023
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	==Myotoxin I from Bothrops moojeni co-crystallized with synthetic inhibitor Varespladib (LY315920)==		==Myotoxin I from Bothrops moojeni co-crystallized with synthetic inhibitor Varespladib (LY315920)==
-	<StructureSection load='7lye' size='340' side='right'caption='[[7lye]]' scene=''>	+	<StructureSection load='7lye' size='340' side='right'caption='[[7lye]], [[Resolution\|resolution]] 1.76Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LYE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LYE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7lye]] is a 4 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=7LYE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LYE FirstGlance]. <br>
-	</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=7lye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lye OCA], [https://pdbe.org/7lye PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lye RCSB], [https://www.ebi.ac.uk/pdbsum/7lye PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lye ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.758Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene>, <scene name='pdbligand=VRD:({3-[amino(oxo)acetyl]-1-benzyl-2-ethyl-1H-indol-4-yl}oxy)acetic+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=7lye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lye OCA], [https://pdbe.org/7lye PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lye RCSB], [https://www.ebi.ac.uk/pdbsum/7lye PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lye ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/PA2H1_BOTMO PA2H1_BOTMO] Snake venom phospholipase A2 homolog that displays local myotoxin and edema-inducing activities and is lethal by intraperitoneal injection.<ref>PMID:10620318</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	BACKGROUND: The treatment for snakebites is early administration of antivenom, which can be highly effective in inhibiting the systemic effects of snake venoms, but is less effective in the treatment of extra-circulatory and local effects. To complement standard-of-care treatments such as antibody-based antivenoms, natural and synthetic small molecules have been proposed for the inhibition of key venom components such as phospholipase A2 (PLA2) and PLA2-like toxins. Varespladib (compound LY315920) is a synthetic molecule developed and clinically tested aiming to block inflammatory cascades of several diseases associated with high PLA2s. Recent studies have demonstrated this molecule is able to potently inhibit snake venom catalytic PLA2 and PLA2-like toxins. METHODS: In vivo and in vitro techniques were used to evaluate the inhibitory effect of varespladib against MjTX-I. X-ray crystallography was used to reveal details of the interaction between these molecules. A new methodology that combines crystallography, mass spectroscopy and phylogenetic data was used to review its primary sequence. RESULTS: Varespladib was able to inhibit the myotoxic and cytotoxic effects of MjTX-I. Structural analysis revealed a particular inhibitory mechanism of MjTX-I when compared to other PLA2-like myotoxin, presenting an oligomeric-independent function. CONCLUSION: Results suggest the effectiveness of varespladib for the inhibition of MjTX-I, in similarity with other PLA2 and PLA2-like toxins. GENERAL SIGNIFICANCE: Varespladib appears to be a promissory molecule in the treatment of local effects led by PLA2 and PLA2-like toxins (oligomeric dependent and independent), indicating that this is a multifunctional or broadly specific inhibitor for different toxins within this superfamily.
		+
		+	The synthetic varespladib molecule is a multi-functional inhibitor for PLA2 and PLA2-like ophidic toxins.,Salvador GHM, Borges RJ, Lomonte B, Lewin MR, Fontes MRM Biochim Biophys Acta Gen Subj. 2021 Jul;1865(7):129913. doi:, 10.1016/j.bbagen.2021.129913. Epub 2021 Apr 16. PMID:33865953<ref>PMID:33865953</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7lye" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phospholipase A2 homolog\|Phospholipase A2 homolog]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Bothrops moojeni]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Borges RJ]]		[[Category: Borges RJ]]
	[[Category: Fontes MRM]]		[[Category: Fontes MRM]]
	[[Category: Salvador GHM]]		[[Category: Salvador GHM]]

OCA at 10:10, 19 May 2021

2021-05-19T10:10:57Z

←Older revision		Revision as of 10:10, 19 May 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7lye ~~is ON HOLD until Paper Publication~~	+	==Myotoxin I from Bothrops moojeni co-crystallized with synthetic inhibitor Varespladib (LY315920)==
-		+	<StructureSection load='7lye' size='340' side='right'caption='[[7lye]]' scene=''>
-	~~Authors~~: ~~Salvador~~, G.H.M., ~~Borges~~, R.J., ~~Fontes, M~~.R.M.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LYE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LYE FirstGlance]. <br>
-	~~Description~~: ~~Myotoxin I from Bothrops moojeni co~~-~~crystallized with synthetic inhibitor Varespladib (LY315920)~~	+	</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=7lye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lye OCA], [https://pdbe.org/7lye PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lye RCSB], [https://www.ebi.ac.uk/pdbsum/7lye PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lye ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Salvador, G.H.M~~]]	+	__TOC__
-	[[Category: ~~Borges, R.J~~]]	+	</StructureSection>
-	[[Category: ~~Fontes, M.R.M~~]]	+	[[Category: Large Structures]]
		+	[[Category: Borges RJ]]
		+	[[Category: Fontes MRM]]
		+	[[Category: Salvador GHM]]

OCA at 05:38, 14 April 2021

2021-04-14T05:38:11Z

←Older revision		Revision as of 05:38, 14 April 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7lye is ON HOLD	+	The entry 7lye is ON HOLD until Paper Publication

	Authors: Salvador, G.H.M., Borges, R.J., Fontes, M.R.M.		Authors: Salvador, G.H.M., Borges, R.J., Fontes, M.R.M.

OCA: Protected "7lye" [edit=sysop:move=sysop]

2021-03-17T05:24:35Z

Protected "7lye" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:24, 17 March 2021

OCA: New page: '''Unreleased structure''' The entry 7lye is ON HOLD Authors: Salvador, G.H.M., Borges, R.J., Fontes, M.R.M. Description: Myotoxin I from Bothrops moojeni co-crystallized with syntheti...

2021-03-17T05:24:34Z

New page: '''Unreleased structure''' The entry 7lye is ON HOLD Authors: Salvador, G.H.M., Borges, R.J., Fontes, M.R.M. Description: Myotoxin I from Bothrops moojeni co-crystallized with syntheti...

New page

'''Unreleased structure'''

The entry 7lye is ON HOLD

Authors: Salvador, G.H.M., Borges, R.J., Fontes, M.R.M.

Description: Myotoxin I from Bothrops moojeni co-crystallized with synthetic inhibitor Varespladib (LY315920)
[[Category: Unreleased Structures]]
[[Category: Salvador, G.H.M]]
[[Category: Borges, R.J]]
[[Category: Fontes, M.R.M]]