7rox - Revision history

OCA at 09:30, 25 October 2023

OCA — Wed, 25 Oct 2023 09:30:00 GMT

←Older revision		Revision as of 09:30, 25 October 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7rox]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bothrops_jararacussu Bothrops jararacussu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ROX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ROX FirstGlance]. <br>		<table><tr><td colspan='2'>[[7rox]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bothrops_jararacussu Bothrops jararacussu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ROX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ROX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=85O:12-methoxy-Nb-methylvoachalotine'>85O</scene></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]] 2.1Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=85O:12-methoxy-Nb-methylvoachalotine'>85O</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=7rox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rox OCA], [https://pdbe.org/7rox PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rox RCSB], [https://www.ebi.ac.uk/pdbsum/7rox PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rox ProSAT]</span></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=7rox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rox OCA], [https://pdbe.org/7rox PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rox RCSB], [https://www.ebi.ac.uk/pdbsum/7rox PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rox ProSAT]</span></td></tr>
	</table>		</table>
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	</div>		</div>
	<div class="pdbe-citations 7rox" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7rox" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phospholipase A2 3D structures\|Phospholipase A2 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:19, 9 November 2022

OCA — Wed, 09 Nov 2022 07:19:08 GMT

←Older revision		Revision as of 07:19, 9 November 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7rox is ~~ON HOLD until Paper~~ Publication	+	==BthTX-I complexed with inhibitor MMV==
		+	<StructureSection load='7rox' size='340' side='right'caption='[[7rox]], [[Resolution\|resolution]] 2.10Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7rox]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bothrops_jararacussu Bothrops jararacussu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ROX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ROX FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=85O:12-methoxy-Nb-methylvoachalotine'>85O</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=7rox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rox OCA], [https://pdbe.org/7rox PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rox RCSB], [https://www.ebi.ac.uk/pdbsum/7rox PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rox ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/PA2H1_BOTJR PA2H1_BOTJR] Snake venom phospholipase A2 homolog that lacks enzymatic activity. Shows local myotoxic activity (PubMed:11018293, PubMed:12079495, PubMed:31906173). Induces inflammation, since it induces edema and leukocytes infiltration (PubMed:11018293, PubMed:31906173). In addition, it induces NLRP3 NLRP3, ASC (PYCARD), caspase-1 (CASP1), and IL-1beta (IL1B) gene expression in the gastrocnemius muscle, showing that it is able to activate NLRP3 inflammasome (PubMed:31906173). It also damages artificial and myoblast membranes by a calcium-independent mechanism, has bactericidal activity, and induces neuromuscular blockade (PubMed:27531710). A model of myotoxic mechanism has been proposed: an apo Lys49-PLA2 is activated by the entrance of a hydrophobic molecule (e.g. fatty acid) at the hydrophobic channel of the protein leading to a reorientation of a monomer (PubMed:27531710) (By similarity). This reorientation causes a transition between 'inactive' to 'active' states, causing alignment of C-terminal and membrane-docking sites (MDoS) side-by-side and putting the membrane-disruption sites (MDiS) in the same plane, exposed to solvent and in a symmetric position for both monomers (PubMed:27531710) (By similarity). The MDoS region stabilizes the toxin on membrane by the interaction of charged residues with phospholipid head groups (PubMed:27531710) (By similarity). Subsequently, the MDiS region destabilizes the membrane with penetration of hydrophobic residues (PubMed:27531710) (By similarity). This insertion causes a disorganization of the membrane, allowing an uncontrolled influx of ions (i.e. calcium and sodium), and eventually triggering irreversible intracellular alterations and cell death (PubMed:27531710) (By similarity).[UniProtKB:I6L8L6]<ref>PMID:11018293</ref> <ref>PMID:11829743</ref> <ref>PMID:12079495</ref> <ref>PMID:17157889</ref> <ref>PMID:17346668</ref> <ref>PMID:18160090</ref> <ref>PMID:27531710</ref> <ref>PMID:3176051</ref> <ref>PMID:31906173</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Snake envenomation is an ongoing global health problem and tropical neglected disease that afflicts millions of people each year. The only specific treatment, antivenom, has several limitations that affects its proper distribution to the victims and its efficacy against local effects, such as myonecrosis. The main responsible for this consequence are the phospholipases A2 (PLA2) and PLA2-like proteins, such as BthTX-I from Bothrops jararacussu. Folk medicine resorts to plants such as Tabernaemontana catharinensis to palliate these and other snakebite effects. Here, we evaluated the effect of its root bark extract and one of its isolated compounds, 12-methoxy-4-methyl-voachalotine (MMV), against the in vitro paralysis and muscle damage induced by BthTX-I. Secondary and quaternary structures of BthTX-I were not modified by the interaction with MMV. Instead, this compound interacted in an unprecedented way with the region inside the toxin hydrophobic channel and promoted a structural change in Val31, loop 58-71 and Membrane Disruption Site. Thus, we hypothesize that MMV inhibits PLA2-like proteins by preventing entrance of fatty acid into the hydrophobic channel. These data may explain the traditional use of T. catharinensis extract and confirm MMV as a promising candidate to complement antivenom or a structural guide to develop more effective inhibitors.

-	~~Authors~~:	+	Structural and functional studies of a snake venom phospholipase A2-like protein complexed to an inhibitor purified from Tabernaemontana catharinensis.,Borges RJ, Cardoso FF, de Carvalho C, de Marino I, Pereira PS, Soares AM, Dal-Pai-Silva M, Uson I, Fontes MRM Biochimie. 2022 Oct 20. pii: S0300-9084(22)00277-2. doi:, 10.1016/j.biochi.2022.10.011. PMID:36273763<ref>PMID:36273763</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 7rox" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Bothrops jararacussu]]
		+	[[Category: Large Structures]]
		+	[[Category: Borges RJ]]
		+	[[Category: De Marino I]]
		+	[[Category: Fontes MRM]]
		+	[[Category: Uson I]]

OCA at 08:14, 15 September 2021

OCA — Wed, 15 Sep 2021 08:14:34 GMT

←Older revision		Revision as of 08:14, 15 September 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Wed, 11 Aug 2021 05:11:49 GMT

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

←Older revision

Revision as of 05:11, 11 August 2021

OCA: New page: '''Unreleased structure''' The entry 7rox is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 11 Aug 2021 05:11:48 GMT

New page: '''Unreleased structure''' The entry 7rox is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7rox is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]