4wtb - Revision history

OCA at 07:36, 27 September 2023

2023-09-27T07:36:29Z

←Older revision		Revision as of 07:36, 27 September 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4wtb]] 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=4WTB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WTB FirstGlance]. <br>		<table><tr><td colspan='2'>[[4wtb]] 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=4WTB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WTB FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.16Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4wtb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wtb OCA], [https://pdbe.org/4wtb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wtb RCSB], [https://www.ebi.ac.uk/pdbsum/4wtb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wtb 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=4wtb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wtb OCA], [https://pdbe.org/4wtb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wtb RCSB], [https://www.ebi.ac.uk/pdbsum/4wtb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wtb ProSAT]</span></td></tr>
	</table>		</table>

OCA at 07:25, 7 April 2023

2023-04-07T07:25:36Z

←Older revision		Revision as of 07:25, 7 April 2023
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	<StructureSection load='4wtb' size='340' side='right'caption='[[4wtb]], [[Resolution\|resolution]] 2.16Å' scene=''>		<StructureSection load='4wtb' size='340' side='right'caption='[[4wtb]], [[Resolution\|resolution]] 2.16Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4wtb]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Bothrops_jararacussu Bothrops jararacussu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WTB OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4WTB FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4wtb]] 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=4WTB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WTB FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3i3h\|3i3h]], [[3iq3\|3iq3]], [[3hzw\|3hzw]], [[3i03\|3i03]], [[3qnl\|3qnl]]~~</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=4wtb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wtb OCA], [https://pdbe.org/4wtb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wtb RCSB], [https://www.ebi.ac.uk/pdbsum/4wtb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wtb ProSAT]</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=4wtb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wtb OCA], [~~http~~://pdbe.org/4wtb PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4wtb RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4wtb PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4wtb ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~PA2B1_BOTJR PA2B1_BOTJR]~~] Snake venom phospholipase A2 homolog that lacks enzymatic activity. In ~~vivo~~, induces ~~muscle necrosis~~, ~~accompanied by polymorphonuclear cell infiltration~~, and ~~edema~~ in the ~~mouse paw~~. ~~Damages~~ artificial and myoblast membranes by a calcium-independent mechanism~~. Has~~ bactericidal activity.<ref>PMID:~~3176051~~</ref> <ref>PMID:~~11018293~~</ref> <ref>PMID:~~11829743~~</ref> <ref>PMID:~~12079495~~</ref> <ref>PMID:17346668</ref> <ref>PMID:18160090</ref> <ref>PMID:~~17157889~~</ref>	+	[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 4wtb" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4wtb" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phospholipase A2 homolog\|Phospholipase A2 homolog]]
	== References ==		== References ==
	<references/>		<references/>
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	[[Category: Bothrops jararacussu]]		[[Category: Bothrops jararacussu]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Borges~~, R J~~]]	+	[[Category: Borges RJ]]
-	[[Category: Fontes~~, M R.M]]~~	+	[[Category: Fontes MRM]]
-	~~[[Category: Bthtx-i]]~~	+
-	~~[[Category: Svpla2-like inhibitor]]~~	+
-	~~[[Category: Toxin~~]]	+

OCA at 06:18, 17 April 2019

2019-04-17T06:18:17Z

←Older revision		Revision as of 06:18, 17 April 2019
Line 1:		Line 1:

	==BthTX-I, a svPLA2s-like toxin, complexed with zinc ions==		==BthTX-I, a svPLA2s-like toxin, complexed with zinc ions==
-	<StructureSection load='4wtb' size='340' side='right' caption='[[4wtb]], [[Resolution\|resolution]] 2.16Å' scene=''>	+	<StructureSection load='4wtb' size='340' side='right'caption='[[4wtb]], [[Resolution\|resolution]] 2.16Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4wtb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bothrops_jararacussu Bothrops jararacussu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WTB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WTB FirstGlance]. <br>		<table><tr><td colspan='2'>[[4wtb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bothrops_jararacussu Bothrops jararacussu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WTB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WTB FirstGlance]. <br>
Line 24:		Line 24:
	</StructureSection>		</StructureSection>
	[[Category: Bothrops jararacussu]]		[[Category: Bothrops jararacussu]]
		+	[[Category: Large Structures]]
	[[Category: Borges, R J]]		[[Category: Borges, R J]]
	[[Category: Fontes, M R.M]]		[[Category: Fontes, M R.M]]

OCA at 09:03, 17 May 2017

2017-05-17T09:03:07Z

←Older revision		Revision as of 09:03, 17 May 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 4wtb is ~~ON HOLD~~	+	==BthTX-I, a svPLA2s-like toxin, complexed with zinc ions==
		+	<StructureSection load='4wtb' size='340' side='right' caption='[[4wtb]], [[Resolution\|resolution]] 2.16Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4wtb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bothrops_jararacussu Bothrops jararacussu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WTB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WTB FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3i3h\|3i3h]], [[3iq3\|3iq3]], [[3hzw\|3hzw]], [[3i03\|3i03]], [[3qnl\|3qnl]]</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=4wtb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wtb OCA], [http://pdbe.org/4wtb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wtb RCSB], [http://www.ebi.ac.uk/pdbsum/4wtb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wtb ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PA2B1_BOTJR PA2B1_BOTJR]] Snake venom phospholipase A2 homolog that lacks enzymatic activity. In vivo, induces muscle necrosis, accompanied by polymorphonuclear cell infiltration, and edema in the mouse paw. Damages artificial and myoblast membranes by a calcium-independent mechanism. Has bactericidal activity.<ref>PMID:3176051</ref> <ref>PMID:11018293</ref> <ref>PMID:11829743</ref> <ref>PMID:12079495</ref> <ref>PMID:17346668</ref> <ref>PMID:18160090</ref> <ref>PMID:17157889</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	BACKGROUND: One of the main challenges in snakebite envenomation treatment is the development of stable, versatile and efficient anti-venom therapies. Local myotoxicity in accidents involving snakes from the Bothrops genus is still a consequence of serum therapy inefficient neutralization that may lead to permanent sequelae in their victims. One of the classes of toxins that participate in muscle necrosis is the PLA2-like proteins. The aim of this work was to investigate the role of zinc ions in the inhibition of PLA2-like proteins and to advance the current knowledge of their action mechanism. METHODS: Myographic and electrophysiological techniques were used to evaluate the inhibitory effect of zinc ions, isothermal titration calorimetry assays were used to measure the affinity between zinc ions and the toxin and X-ray crystallography was used to reveal details of this interaction. RESULTS: We demonstrated that zinc ions can effectively inhibit the toxin by the interaction with two different sites, which are related to two different mechanism of inhibition: preventing membrane disruption and impairing the toxin state transition. Furthermore, structural study presented here included an additional step in the current myotoxic mechanism improving the comprehension of the allosteric transition that PLA2-like proteins undergo to exert their function. CONCLUSIONS: Our findings show that zinc ions are inhibitors of PLA2-like proteins and suggest two different mechanisms of inhibition for these ions. GENERAL SIGNIFICANCE: Zinc is a new candidate that can assist in anti-venom treatments and can promote the design of new and even more accurate structure-based inhibitors for PLA2-like proteins.

-	~~Authors~~: Borges, R.J., ~~Fontes, M~~.R.M.	+	Functional and structural studies of a Phospholipase A2-like protein complexed to zinc ions: Insights on its myotoxicity and inhibition mechanism.,Borges RJ, Cardoso FF, Fernandes CA, Dreyer TR, de Moraes DS, Floriano RS, Rodrigues-Simioni L, Fontes MR Biochim Biophys Acta. 2017 Jan;1861(1 Pt A):3199-3209. doi:, 10.1016/j.bbagen.2016.08.003. Epub 2016 Aug 13. PMID:27531710<ref>PMID:27531710</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Fontes, M.R.M]]	+	<div class="pdbe-citations 4wtb" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Borges, R.J~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Bothrops jararacussu]]
		+	[[Category: Borges, R J]]
		+	[[Category: Fontes, M R.M]]
		+	[[Category: Bthtx-i]]
		+	[[Category: Svpla2-like inhibitor]]
		+	[[Category: Toxin]]

OCA at 19:57, 24 December 2014

2014-12-24T19:57:20Z

←Older revision		Revision as of 19:57, 24 December 2014
Line 5:		Line 5:
	Authors: Borges, R.J., Fontes, M.R.M.		Authors: Borges, R.J., Fontes, M.R.M.

-	Description:	+	Description:
		+	[[Category: Unreleased Structures]]
		+	[[Category: Fontes, M.R.M]]
		+	[[Category: Borges, R.J]]

OCA: Protected "4wtb" [edit=sysop:move=sysop]

2014-11-05T08:08:37Z

Protected "4wtb" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:08, 5 November 2014

OCA: New page: '''Unreleased structure''' The entry 4wtb is ON HOLD Authors: Borges, R.J., Fontes, M.R.M. Description:

2014-11-05T08:08:36Z

New page: '''Unreleased structure''' The entry 4wtb is ON HOLD Authors: Borges, R.J., Fontes, M.R.M. Description:

New page

'''Unreleased structure'''

The entry 4wtb is ON HOLD

Authors: Borges, R.J., Fontes, M.R.M.

Description: