1av3
From Proteopedia
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| - | + | ==POTASSIUM CHANNEL BLOCKER KAPPA CONOTOXIN PVIIA FROM C. PURPURASCENS, NMR, 20 STRUCTURES== | |
| - | + | <StructureSection load='1av3' size='340' side='right'caption='[[1av3]]' scene=''> | |
| - | | | + | == Structural highlights == |
| - | | | + | <table><tr><td colspan='2'>[[1av3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_purpurascens Conus purpurascens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AV3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AV3 FirstGlance]. <br> |
| - | + | </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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</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=1av3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1av3 OCA], [https://pdbe.org/1av3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1av3 RCSB], [https://www.ebi.ac.uk/pdbsum/1av3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1av3 ProSAT]</span></td></tr> | |
| - | + | </table> | |
| - | + | == Function == | |
| - | + | [https://www.uniprot.org/uniprot/O17A_CONPU O17A_CONPU] Kappa-conotoxins bind and inhibit voltage-gated potassium channels (Kv). This toxin inhibits the drosophila Shaker channel (IC(50)=57-80 nM) (PubMed:12074021, PubMed:10818087, PubMed:27093300). In vivo, when tested in fish, this toxin induces hyperactivity, followed by continuous contraction and extension of major fins, without immobilization or death (PubMed:9417043, PubMed:12074021). Injection of this peptide together with the delta-conotoxin PVIA causes the sudden tetanus of prey (STOP) syndrome, which is a single, lethal 'fin-pop' in envenomed fish (PubMed:9417043, PubMed:12074021). When tested in mice, induces hyperactivity (PubMed:9417043).<ref>PMID:10398696</ref> <ref>PMID:10818087</ref> <ref>PMID:12023223</ref> <ref>PMID:12074021</ref> <ref>PMID:27093300</ref> <ref>PMID:9417043</ref> | |
| - | + | <div style="background-color:#fffaf0;"> | |
| - | + | == Publication Abstract from PubMed == | |
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BACKGROUND: kappa-PVIIA is a 27-residue polypeptide isolated from the venom of Conus purpurascens and is the first member of a new class of conotoxins that block potassium channels. By comparison to other ion channels of eukaryotic cell membranes, voltage-sensitive potassium channels are relatively simple and methodology has been developed for mapping their interactions with small-peptide toxins. PVIIA, therefore, is a valuable new probe of potassium channel structure. This study of the solution structure and mode of channel binding of PVIIA forms the basis for mapping the interacting residues at the conotoxin-ion channel interface. RESULTS: The three-dimensional structure of PVIIA resembles the triple-stranded beta sheet/cystine-knot motif formed by a number of toxic and inhibitory peptides. Subtle structural differences, predominantly in loops 2 and 4, are observed between PVIIA and other conotoxins with similar structural frameworks, however. Electrophysiological binding data suggest that PVIIA blocks channel currents by binding in a voltage-sensitive manner to the external vestibule and occluding the pore. Comparison of the electrostatic surface of PVIIA with that of the well-characterised potassium channel blocker charybdotoxin suggests a likely binding orientation for PVIIA. CONCLUSIONS: Although the structure of PVIIA is considerably different to that of the alphaK scorpion toxins, it has a similar mechanism of channel blockade. On the basis of a comparison of the structures of PVIIA and charybdotoxin, we suggest that Lys19 of PVIIA is the residue which is responsible for physically occluding the pore of the potassium channel. | BACKGROUND: kappa-PVIIA is a 27-residue polypeptide isolated from the venom of Conus purpurascens and is the first member of a new class of conotoxins that block potassium channels. By comparison to other ion channels of eukaryotic cell membranes, voltage-sensitive potassium channels are relatively simple and methodology has been developed for mapping their interactions with small-peptide toxins. PVIIA, therefore, is a valuable new probe of potassium channel structure. This study of the solution structure and mode of channel binding of PVIIA forms the basis for mapping the interacting residues at the conotoxin-ion channel interface. RESULTS: The three-dimensional structure of PVIIA resembles the triple-stranded beta sheet/cystine-knot motif formed by a number of toxic and inhibitory peptides. Subtle structural differences, predominantly in loops 2 and 4, are observed between PVIIA and other conotoxins with similar structural frameworks, however. Electrophysiological binding data suggest that PVIIA blocks channel currents by binding in a voltage-sensitive manner to the external vestibule and occluding the pore. Comparison of the electrostatic surface of PVIIA with that of the well-characterised potassium channel blocker charybdotoxin suggests a likely binding orientation for PVIIA. CONCLUSIONS: Although the structure of PVIIA is considerably different to that of the alphaK scorpion toxins, it has a similar mechanism of channel blockade. On the basis of a comparison of the structures of PVIIA and charybdotoxin, we suggest that Lys19 of PVIIA is the residue which is responsible for physically occluding the pore of the potassium channel. | ||
| - | + | Solution structure and proposed binding mechanism of a novel potassium channel toxin kappa-conotoxin PVIIA.,Scanlon MJ, Naranjo D, Thomas L, Alewood PF, Lewis RJ, Craik DJ Structure. 1997 Dec 15;5(12):1585-97. PMID:9438859<ref>PMID:9438859</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 1av3" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Conus purpurascens]] | [[Category: Conus purpurascens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: Alewood | + | [[Category: Alewood PF]] |
| - | [[Category: Craik | + | [[Category: Craik DJ]] |
| - | [[Category: Lewis | + | [[Category: Lewis RJ]] |
| - | [[Category: Naranjo | + | [[Category: Naranjo D]] |
| - | [[Category: Scanlon | + | [[Category: Scanlon MJ]] |
| - | [[Category: Thomas | + | [[Category: Thomas L]] |
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Current revision
POTASSIUM CHANNEL BLOCKER KAPPA CONOTOXIN PVIIA FROM C. PURPURASCENS, NMR, 20 STRUCTURES
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