2i61

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{{Seed}}
 
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[[Image:2i61.png|left|200px]]
 
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==Depressant anti-insect neurotoxin, LqhIT2 from Leiurus quinquestriatus hebraeus==
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The line below this paragraph, containing "STRUCTURE_2i61", creates the "Structure Box" on the page.
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<StructureSection load='2i61' size='340' side='right'caption='[[2i61]], [[Resolution|resolution]] 1.20&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'>[[2i61]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leiurus_hebraeus Leiurus hebraeus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I61 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I61 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]] 1.2&#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=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=CO2:CARBON+DIOXIDE'>CO2</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=LI:LITHIUM+ION'>LI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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{{STRUCTURE_2i61| PDB=2i61 | 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=2i61 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i61 OCA], [https://pdbe.org/2i61 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i61 RCSB], [https://www.ebi.ac.uk/pdbsum/2i61 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i61 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/SIX2_LEIHE SIX2_LEIHE] Depressant insect beta-toxins cause a transient contraction paralysis followed by a slow flaccid paralysis. They bind voltage-independently at site-4 of sodium channels (Nav) and shift the voltage of activation toward more negative potentials thereby affecting sodium channel activation and promoting spontaneous and repetitive firing. This toxin is active only on insects.<ref>PMID:9275012</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/i6/2i61_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=2i61 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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Scorpion depressant beta-toxins show high preference for insect voltage-gated sodium channels (Na(v)s) and modulate their activation. Although their pharmacological and physiological effects were described, their three-dimensional structure and bioactive surface have never been determined. We utilized an efficient system for expression of the depressant toxin LqhIT2 (from Leiurus quinquestriatushebraeus), mutagenized its entire exterior, and determined its X-ray structure at 1.2 A resolution. The toxin molecule is composed of a conserved cysteine-stabilized alpha/beta-core (core-globule), and perpendicular to it an entity constituted from the N and C-terminal regions (NC-globule). The surface topology and overall hydrophobicity of the groove between the core and NC-globules (N-groove) is important for toxin activity and plays a role in selectivity to insect Na(v)s. The N-groove is flanked by Glu24 and Tyr28, which belong to the "pharmacophore" of scorpion beta-toxins, and by the side-chains of Trp53 and Asn58 that are important for receptor site recognition. Substitution of Ala13 by Trp in the N-groove uncoupled activity from binding, suggesting that this region of the molecule is also involved in "voltage-sensor trapping", the mode of action that typifies scorpion beta-toxins. The involvement of the N-groove in recognition of the receptor site, which seems to require a defined topology, as well as in sensor trapping, which involves interaction with a moving channel region, is puzzling. On the basis of the mutagenesis studies we hypothesize that following binding to the receptor site, the toxin undergoes a conformational change at the N-groove region that facilitates the trapping of the voltage-sensor in its activated position.
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===Depressant anti-insect neurotoxin, LqhIT2 from Leiurus quinquestriatus hebraeus===
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X-ray structure and mutagenesis of the scorpion depressant toxin LqhIT2 reveals key determinants crucial for activity and anti-insect selectivity.,Karbat I, Turkov M, Cohen L, Kahn R, Gordon D, Gurevitz M, Frolow F J Mol Biol. 2007 Feb 16;366(2):586-601. Epub 2006 Nov 10. PMID:17166514<ref>PMID:17166514</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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The line below this paragraph, {{ABSTRACT_PUBMED_17166514}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 2i61" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 17166514 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_17166514}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Large Structures]]
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2I61 is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Leiurus_quinquestriatus_hebraeus Leiurus quinquestriatus hebraeus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I61 OCA].
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[[Category: Leiurus hebraeus]]
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[[Category: Frolow F]]
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==Reference==
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[[Category: Gordon D]]
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<ref group="xtra">PMID:17166514</ref><references group="xtra"/>
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[[Category: Gurevitz M]]
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[[Category: Leiurus quinquestriatus hebraeus]]
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[[Category: Karbat I]]
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[[Category: Frolow, F.]]
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[[Category: Turkov M]]
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[[Category: Gordon, D.]]
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[[Category: Gurevitz, M.]]
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[[Category: Karbat, I.]]
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[[Category: Turkov, M.]]
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[[Category: Anti-insect]]
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[[Category: Depressant]]
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[[Category: Scorpion toxin]]
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[[Category: Sodium channel modifer]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 13:58:24 2009''
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Current revision

Depressant anti-insect neurotoxin, LqhIT2 from Leiurus quinquestriatus hebraeus

PDB ID 2i61

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