3cxi

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{{Seed}}
 
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[[Image:3cxi.png|left|200px]]
 
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==Structure of BthTX-I complexed with alpha-tocopherol==
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The line below this paragraph, containing "STRUCTURE_3cxi", creates the "Structure Box" on the page.
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<StructureSection load='3cxi' size='340' side='right'caption='[[3cxi]], [[Resolution|resolution]] 1.83&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3cxi]] 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=3CXI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CXI FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.83&#8491;</td></tr>
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<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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VIT:VITAMIN+E'>VIT</scene></td></tr>
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{{STRUCTURE_3cxi| PDB=3cxi | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3cxi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cxi OCA], [https://pdbe.org/3cxi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cxi RCSB], [https://www.ebi.ac.uk/pdbsum/3cxi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cxi ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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 (By similarity) (PubMed:27531710). 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 (By similarity) (PubMed:27531710). The MDoS region stabilizes the toxin on membrane by the interaction of charged residues with phospholipid head groups (By similarity) (PubMed:27531710). Subsequently, the MDiS region destabilizes the membrane with penetration of hydrophobic residues (By similarity) (PubMed:27531710). 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 (By similarity) (PubMed:27531710).[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cx/3cxi_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3cxi ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Phospholipases A(2) (PLA(2)s) are membrane-associated enzymes that hydrolyze phospholipids at the sn-2 position, releasing lysophospholipids and free fatty acids. Phospholipase A(2) homologues (Lys49-PLA(2)s) are highly myotoxic and cause extensive tissue damage despite not showing measurable catalytic activity. They are found in different snake venoms and represent one third of bothropic venom composition. The importance of these toxins during envenomation is related to the pronounced local myotoxic effect they induce since this effect is not neutralized by serum therapy. We present herein three structures of Lys49-PLA(2)s from Bothrops genus snake venom crystallized under the same conditions, two of which were grown in the presence of alpha-tocopherol (vitamin E). Comparative structural analysis of these and other Lys49-PLA(2)s showed two different patterns of oligomeric conformation that are related to the presence or absence of ligands in the hydrophobic channel. This work also confirms the biological dimer indicated by recent studies in which both C-termini are in the dimeric interface. In this configuration, we propose that the myotoxic site of these toxins is composed by the Lys 20, Lys115 and Arg118 residues. For the first time, a residue from the short-helix (Lys20) is suggested as a member of this site and the importance of Tyr119 residue to myotoxicity of bothropic Lys49-PLA(2)s is also discussed. These results support a complete hypothesis for these PLA(2)s myotoxic activity consistent with all findings on bothropic Lys49-PLA(2)s studied up to this moment, including crystallographic, bioinformatics, biochemical and biophysical data.
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===Structure of BthTX-I complexed with alpha-tocopherol===
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Comparative structural studies on Lys49-phospholipases A(2) from Bothrops genus reveal their myotoxic site.,dos Santos JI, Soares AM, Fontes MR J Struct Biol. 2009 Aug;167(2):106-16. Epub 2009 May 3. PMID:19401234<ref>PMID:19401234</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3cxi" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_19401234}}, adds the Publication Abstract to the page
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*[[Phospholipase A2 3D structures|Phospholipase A2 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 19401234 is the PubMed ID number.
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*[[Phospholipase A2 homolog|Phospholipase A2 homolog]]
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== References ==
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{{ABSTRACT_PUBMED_19401234}}
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<references/>
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__TOC__
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==About this Structure==
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</StructureSection>
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3CXI is a 2 chains structure of sequences 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=3CXI OCA].
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==Reference==
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<ref group="xtra">PMID:19401234</ref><references group="xtra"/>
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[[Category: Bothrops jararacussu]]
[[Category: Bothrops jararacussu]]
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[[Category: Fontes, M R.M.]]
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[[Category: Large Structures]]
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[[Category: Santos, J I.dos.]]
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[[Category: Fontes MRM]]
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[[Category: Bothrops jaracussu]]
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[[Category: Dos Santos JI]]
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[[Category: Lys49-pla2]]
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[[Category: Myotoxin]]
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[[Category: Phospholipase a2]]
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[[Category: Secreted]]
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[[Category: Snake venom]]
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[[Category: X-ray crystallography]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jan 18 09:05:39 2010''
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Current revision

Structure of BthTX-I complexed with alpha-tocopherol

PDB ID 3cxi

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