|
|
| (16 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| - | [[Image:1kcp.jpg|left|200px]]<br /><applet load="1kcp" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1kcp" /> | |
| - | '''3D STRUCTURE OF K-CONOTOXIN PVIIA, A NOVEL POTASSIUM CHANNEL-BLOCKING TOXIN FROM CONE SNAILS, NMR, 22 STRUCTURES'''<br /> | |
| | | | |
| - | ==Overview== | + | ==3D STRUCTURE OF K-CONOTOXIN PVIIA, A NOVEL POTASSIUM CHANNEL-BLOCKING TOXIN FROM CONE SNAILS, NMR, 22 STRUCTURES== |
| - | kappa-Conotoxin PVIIA from the venom of Conus purpurascens is the first, cone snail toxin that was described to block potassium channels. We, synthesized chemically this toxin and showed that its disulfide bridge, pattern is similar to those of omega- and delta-conotoxins., kappa-conotoxin competes with radioactive alpha-dendrotoxin for binding to, rat brain synaptosomes, confirming its capacity to bind to potassium, channels; however, it behaves as a weak competitor. The three-dimensional, structure of kappa-conotoxin PVIIA, as elucidated by NMR spectroscopy and, molecular modeling, comprises two large parallel loops stabilized by a, triple-stranded antiparallel beta-sheet and three disulfide bridges. The, overall fold of kappa-conotoxin is similar to that of calcium, channel-blocking omega-conotoxins but differs from those of potassium, channel-blocking toxins from sea anemones, scorpions, and snakes. Local, topographies of kappa-conotoxin PVIIA that might account for its capacity, to recognize Kv1-type potassium channels are discussed. | + | <StructureSection load='1kcp' size='340' side='right'caption='[[1kcp]]' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1kcp]] 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=1KCP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KCP FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 22 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>, <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=1kcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kcp OCA], [https://pdbe.org/1kcp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kcp RCSB], [https://www.ebi.ac.uk/pdbsum/1kcp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kcp 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 == |
| | + | kappa-Conotoxin PVIIA from the venom of Conus purpurascens is the first cone snail toxin that was described to block potassium channels. We synthesized chemically this toxin and showed that its disulfide bridge pattern is similar to those of omega- and delta-conotoxins. kappa-conotoxin competes with radioactive alpha-dendrotoxin for binding to rat brain synaptosomes, confirming its capacity to bind to potassium channels; however, it behaves as a weak competitor. The three-dimensional structure of kappa-conotoxin PVIIA, as elucidated by NMR spectroscopy and molecular modeling, comprises two large parallel loops stabilized by a triple-stranded antiparallel beta-sheet and three disulfide bridges. The overall fold of kappa-conotoxin is similar to that of calcium channel-blocking omega-conotoxins but differs from those of potassium channel-blocking toxins from sea anemones, scorpions, and snakes. Local topographies of kappa-conotoxin PVIIA that might account for its capacity to recognize Kv1-type potassium channels are discussed. |
| | | | |
| - | ==About this Structure==
| + | Three-dimensional structure of kappa-conotoxin PVIIA, a novel potassium channel-blocking toxin from cone snails.,Savarin P, Guenneugues M, Gilquin B, Lamthanh H, Gasparini S, Zinn-Justin S, Menez A Biochemistry. 1998 Apr 21;37(16):5407-16. PMID:9548922<ref>PMID:9548922</ref> |
| - | 1KCP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Conus_purpurascens Conus purpurascens] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1KCP OCA].
| + | |
| | | | |
| - | ==Reference==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | Three-dimensional structure of kappa-conotoxin PVIIA, a novel potassium channel-blocking toxin from cone snails., Savarin P, Guenneugues M, Gilquin B, Lamthanh H, Gasparini S, Zinn-Justin S, Menez A, Biochemistry. 1998 Apr 21;37(16):5407-16. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9548922 9548922]
| + | </div> |
| | + | <div class="pdbe-citations 1kcp" style="background-color:#fffaf0;"></div> |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Conus purpurascens]] | | [[Category: Conus purpurascens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Gasparini, S.]] | + | [[Category: Gasparini S]] |
| - | [[Category: Gilquin, B.]] | + | [[Category: Gilquin B]] |
| - | [[Category: Guenneugues, M.]] | + | [[Category: Guenneugues M]] |
| - | [[Category: Lamthanh, H.]] | + | [[Category: Lamthanh H]] |
| - | [[Category: Menez, A.]] | + | [[Category: Menez A]] |
| - | [[Category: Savarin, P.]] | + | [[Category: Savarin P]] |
| - | [[Category: Zinn-Justin, S.]] | + | [[Category: Zinn-Justin S]] |
| - | [[Category: NH2]]
| + | |
| - | [[Category: neurotoxin]]
| + | |
| - | [[Category: potassium channel inhibitor]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 19:03:54 2007''
| + | |
| Structural highlights
Function
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).[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
kappa-Conotoxin PVIIA from the venom of Conus purpurascens is the first cone snail toxin that was described to block potassium channels. We synthesized chemically this toxin and showed that its disulfide bridge pattern is similar to those of omega- and delta-conotoxins. kappa-conotoxin competes with radioactive alpha-dendrotoxin for binding to rat brain synaptosomes, confirming its capacity to bind to potassium channels; however, it behaves as a weak competitor. The three-dimensional structure of kappa-conotoxin PVIIA, as elucidated by NMR spectroscopy and molecular modeling, comprises two large parallel loops stabilized by a triple-stranded antiparallel beta-sheet and three disulfide bridges. The overall fold of kappa-conotoxin is similar to that of calcium channel-blocking omega-conotoxins but differs from those of potassium channel-blocking toxins from sea anemones, scorpions, and snakes. Local topographies of kappa-conotoxin PVIIA that might account for its capacity to recognize Kv1-type potassium channels are discussed.
Three-dimensional structure of kappa-conotoxin PVIIA, a novel potassium channel-blocking toxin from cone snails.,Savarin P, Guenneugues M, Gilquin B, Lamthanh H, Gasparini S, Zinn-Justin S, Menez A Biochemistry. 1998 Apr 21;37(16):5407-16. PMID:9548922[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Terlau H, Boccaccio A, Olivera BM, Conti F. The block of Shaker K+ channels by kappa-conotoxin PVIIA is state dependent. J Gen Physiol. 1999 Jul;114(1):125-40. PMID:10398696
- ↑ Jacobsen RB, Koch ED, Lange-Malecki B, Stocker M, Verhey J, Van Wagoner RM, Vyazovkina A, Olivera BM, Terlau H. Single amino acid substitutions in kappa-conotoxin PVIIA disrupt interaction with the shaker K+ channel. J Biol Chem. 2000 Aug 11;275(32):24639-44. doi: 10.1074/jbc.C900990199. PMID:10818087 doi:http://dx.doi.org/10.1074/jbc.C900990199
- ↑ Naranjo D. Inhibition of single Shaker K channels by kappa-conotoxin-PVIIA. Biophys J. 2002 Jun;82(6):3003-11. PMID:12023223 doi:http://dx.doi.org/S0006-3495(02)75641-5
- ↑ Terlau H, Shon KJ, Grilley M, Stocker M, Stuhmer W, Olivera BM. Strategy for rapid immobilization of prey by a fish-hunting marine snail. Nature. 1996 May 9;381(6578):148-51. PMID:12074021 doi:http://dx.doi.org/10.1038/381148a0
- ↑ Kwon S, Bosmans F, Kaas Q, Cheneval O, Conibear AC, Rosengren KJ, Wang CK, Schroeder CI, Craik DJ. Efficient enzymatic cyclization of an inhibitory cystine knot-containing peptide. Biotechnol Bioeng. 2016 Oct;113(10):2202-12. doi: 10.1002/bit.25993. Epub 2016, Aug 9. PMID:27093300 doi:http://dx.doi.org/10.1002/bit.25993
- ↑ Shon KJ, Stocker M, Terlau H, Stuhmer W, Jacobsen R, Walker C, Grilley M, Watkins M, Hillyard DR, Gray WR, Olivera BM. kappa-Conotoxin PVIIA is a peptide inhibiting the shaker K+ channel. J Biol Chem. 1998 Jan 2;273(1):33-8. PMID:9417043
- ↑ Savarin P, Guenneugues M, Gilquin B, Lamthanh H, Gasparini S, Zinn-Justin S, Menez A. Three-dimensional structure of kappa-conotoxin PVIIA, a novel potassium channel-blocking toxin from cone snails. Biochemistry. 1998 Apr 21;37(16):5407-16. PMID:9548922 doi:10.1021/bi9730341
|
