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| | ==Solution structure of insectidal toxin delta-paluIT2-NH2== | | ==Solution structure of insectidal toxin delta-paluIT2-NH2== |
| - | <StructureSection load='1v91' size='340' side='right'caption='[[1v91]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1v91' size='340' side='right'caption='[[1v91]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1v91]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Paracoelotes_luctuosus Paracoelotes luctuosus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V91 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1V91 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1v91]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pireneitega_luctuosa Pireneitega luctuosa]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V91 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1V91 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1v90|1v90]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=1v91 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1v91 OCA], [https://pdbe.org/1v91 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1v91 RCSB], [https://www.ebi.ac.uk/pdbsum/1v91 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1v91 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=1v91 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1v91 OCA], [https://pdbe.org/1v91 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1v91 RCSB], [https://www.ebi.ac.uk/pdbsum/1v91 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1v91 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/TXDP2_PIRLC TXDP2_PIRLC]] Insecticidal toxin. Lethal to lepidopteran larvae. No adverse affects when intracerebroventricularly injected in mice at a dose of 0.2 ug but causes reversible paralysis of legs when injected intracerebroventricularly in mice at a dose of 2.0 ug. Binds to site 4 of insect voltage-gated sodium channel (Nav) and inhibits channel inactivation.<ref>PMID:10971590</ref> <ref>PMID:15683238</ref>
| + | [https://www.uniprot.org/uniprot/T3D1B_PIRLC T3D1B_PIRLC] Insecticidal toxin. Binds to site 4 of insect voltage-gated sodium channel (Nav) and inhibits channel inactivation. In vivo, it lethal to lepidopteran larvae. Has no adverse affects when intracerebroventricularly injected in mice at a dose of 0.2 ug, but causes reversible paralysis of legs when injected intracerebroventricularly in mice at a dose of 2.0 ug.<ref>PMID:10971590</ref> <ref>PMID:15683238</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v9/1v91_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v9/1v91_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Paracoelotes luctuosus]] | + | [[Category: Pireneitega luctuosa]] |
| - | [[Category: Bosmans, F]] | + | [[Category: Bosmans F]] |
| - | [[Category: Chagot, B]] | + | [[Category: Chagot B]] |
| - | [[Category: Corzo, G]] | + | [[Category: Corzo G]] |
| - | [[Category: Darbon, H]] | + | [[Category: Darbon H]] |
| - | [[Category: Ferrat, G]] | + | [[Category: Ferrat G]] |
| - | [[Category: Nakajima, T]] | + | [[Category: Nakajima T]] |
| - | [[Category: Pimentel, C]] | + | [[Category: Pimentel C]] |
| - | [[Category: Tytgat, J]] | + | [[Category: Tytgat J]] |
| - | [[Category: Amidation]]
| + | |
| - | [[Category: Ionic channel inhibitor]]
| + | |
| - | [[Category: Neurotoxin]]
| + | |
| - | [[Category: Sodium channel inhibitor]]
| + | |
| - | [[Category: Toxin]]
| + | |
| Structural highlights
Function
T3D1B_PIRLC Insecticidal toxin. Binds to site 4 of insect voltage-gated sodium channel (Nav) and inhibits channel inactivation. In vivo, it lethal to lepidopteran larvae. Has no adverse affects when intracerebroventricularly injected in mice at a dose of 0.2 ug, but causes reversible paralysis of legs when injected intracerebroventricularly in mice at a dose of 2.0 ug.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Delta-paluIT1 and delta-paluIT2 are toxins purified from the venom of the spider Paracoelotes luctuosus. Similar in sequence to mu-agatoxins from Agelenopsis aperta, their pharmacological target is the voltage-gated insect sodium channel, of which they alter the inactivation properties in a way similar to alpha-scorpion toxins, but they bind on site 4 in a way similar to beta-scorpion toxins. We determined the solution structure of the two toxins by use of two-dimensional nuclear magnetic resonance (NMR) techniques followed by distance geometry and molecular dynamics. The structures of delta-paluIT1 and delta-paluIT2 belong to the inhibitory cystine knot structural family, i.e. a compact disulfide-bonded core from which four loops emerge. Delta-paluIT1 and delta-paluIT2 contain respectively two- and three-stranded anti-parallel beta-sheets as unique secondary structure. We compare the structure and the electrostatic anisotropy of those peptides to other sodium and calcium channel toxins, analyze the topological juxtaposition of key functional residues, and conclude that the recognition of insect voltage-gated sodium channels by these toxins involves the beta-sheet, in addition to loops I and IV. Besides the position of culprit residues on the molecular surface, difference in dipolar moment orientation is another determinant of receptor binding and biological activity differences. We also demonstrate by electrophysiological experiments on the cloned insect voltage-gated sodium channel, para, heterologuously co-expressed with the tipE subunit in Xenopus laevis oocytes, that delta-paluIT1 and delta-paluIT2 procure an increase of Na+ current. delta-PaluIT1-OH seems to have less effect when the same concentrations are used.
Solution structure of two insect-specific spider toxins and their pharmacological interaction with the insect voltage-gated Na+ channel.,Ferrat G, Bosmans F, Tytgat J, Pimentel C, Chagot B, Gilles N, Nakajima T, Darbon H, Corzo G Proteins. 2005 May 1;59(2):368-79. PMID:15726637[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Corzo G, Escoubas P, Stankiewicz M, Pelhate M, Kristensen CP, Nakajima T. Isolation, synthesis and pharmacological characterization of delta-palutoxins IT, novel insecticidal toxins from the spider Paracoelotes luctuosus (Amaurobiidae). Eur J Biochem. 2000 Sep;267(18):5783-95. PMID:10971590
- ↑ Corzo G, Escoubas P, Villegas E, Karbat I, Gordon D, Gurevitz M, Nakajima T, Gilles N. A spider toxin that induces a typical effect of scorpion alpha-toxins but competes with beta-toxins on binding to insect sodium channels. Biochemistry. 2005 Feb 8;44(5):1542-9. PMID:15683238 doi:http://dx.doi.org/10.1021/bi048434k
- ↑ Ferrat G, Bosmans F, Tytgat J, Pimentel C, Chagot B, Gilles N, Nakajima T, Darbon H, Corzo G. Solution structure of two insect-specific spider toxins and their pharmacological interaction with the insect voltage-gated Na+ channel. Proteins. 2005 May 1;59(2):368-79. PMID:15726637 doi:10.1002/prot.20424
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