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| | ==N-TYPE CALCIUM CHANNEL BLOCKER, OMEGA-CONOTOXIN MVIIA, NMR, 15 STRUCTURES== | | ==N-TYPE CALCIUM CHANNEL BLOCKER, OMEGA-CONOTOXIN MVIIA, NMR, 15 STRUCTURES== |
| - | <StructureSection load='1mvi' size='340' side='right'caption='[[1mvi]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> | + | <StructureSection load='1mvi' size='340' side='right'caption='[[1mvi]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1mvi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conma Conma]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MVI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MVI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1mvi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_magus Conus magus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MVI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MVI 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='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=1mvi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mvi OCA], [https://pdbe.org/1mvi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mvi RCSB], [https://www.ebi.ac.uk/pdbsum/1mvi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mvi 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=1mvi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mvi OCA], [https://pdbe.org/1mvi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mvi RCSB], [https://www.ebi.ac.uk/pdbsum/1mvi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mvi ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CO17A_CONMA CO17A_CONMA]] Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels. This toxin blocks N-type calcium channels (Cav2.2/CACNA1B).
| + | [https://www.uniprot.org/uniprot/O17A_CONMA O17A_CONMA] Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels. This toxin blocks Cav2.2/CACNA1B calcium channels (IC(50)=0.67-208 nM) (PubMed:7826361, PubMed:26344359, PubMed:34589389). It acts by neutralizing the outer electronegativity and sterically hindering the ion access path to the entrance of the channel selectivity filter (PubMed:34234349). It also shows antiproliferative effects on different glioma cell lines (M059J, U-138MG and U-251MG) (PubMed:28202361). In vivo, is lethal to fish (PubMed:26344359, PubMed:34589389). In vivo, injection into mammals induces adverse effects, such as tremor, diminution of spontaneous locomotor activity and bad coordinated locomotion (PubMed:26344359). In addition, it causes reduction of tumor area in the mouse glioma model, that is induced by the orthotopic injection of GL261 cells into the brain (PubMed:28202361).<ref>PMID:26344359</ref> <ref>PMID:34234349</ref> <ref>PMID:7826361</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Conma]] | + | [[Category: Conus magus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Alewood, P F]] | + | [[Category: Alewood PF]] |
| - | [[Category: Craik, D J]] | + | [[Category: Craik DJ]] |
| - | [[Category: Lewis, R J]] | + | [[Category: Lewis RJ]] |
| - | [[Category: Nielsen, K J]] | + | [[Category: Nielsen KJ]] |
| - | [[Category: Thomas, L]] | + | [[Category: Thomas L]] |
| - | [[Category: Conus magus peptide specific to n-type voltage sensitive calcium channel]]
| + | |
| - | [[Category: Neurotoxin]]
| + | |
| Structural highlights
Function
O17A_CONMA Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels. This toxin blocks Cav2.2/CACNA1B calcium channels (IC(50)=0.67-208 nM) (PubMed:7826361, PubMed:26344359, PubMed:34589389). It acts by neutralizing the outer electronegativity and sterically hindering the ion access path to the entrance of the channel selectivity filter (PubMed:34234349). It also shows antiproliferative effects on different glioma cell lines (M059J, U-138MG and U-251MG) (PubMed:28202361). In vivo, is lethal to fish (PubMed:26344359, PubMed:34589389). In vivo, injection into mammals induces adverse effects, such as tremor, diminution of spontaneous locomotor activity and bad coordinated locomotion (PubMed:26344359). In addition, it causes reduction of tumor area in the mouse glioma model, that is induced by the orthotopic injection of GL261 cells into the brain (PubMed:28202361).[1] [2] [3]
Publication Abstract from PubMed
The omega-conotoxins are a set of structurally related peptides that have a wide range of specificities for different subtypes of the voltage-sensitive calcium channel (VSCC). To understand their VSCC subtype differentiation we studied the structure of two naturally occurring omega-conotoxins, MVIIA (specific to N-type) and SVIB (specific to P/Q-type) and a synthetic hybrid, SNX-202, which has altered specificities to both VSCC subtypes. The secondary structures of the three peptides are almost identical, consisting of a triple-stranded beta-sheet and several turns. A comparison of NMR data emphasizes the structural similarities between the peptides and highlights some minor structural differences. In the three-dimensional structures of SVIB and MVIIA these are manifested as orientational differences between two key loops. The structural rigidity of MVIIA was also examined. H alpha shifts are similar in a range of solvents, indicating that there are no solvent-induced changes in structure. The omega-conotoxins form a consensus structure despite differences in sequence and VSCC subtype specificity. This indicates that the omega-conotoxin macrosites for the N/P/Q-subfamily of VSCCs are related, with specificity for receptor targets being conferred by the positions of functional side-chains on the surface of the peptides.
A consensus structure for omega-conotoxins with different selectivities for voltage-sensitive calcium channel subtypes: comparison of MVIIA, SVIB and SNX-202.,Nielsen KJ, Thomas L, Lewis RJ, Alewood PF, Craik DJ J Mol Biol. 1996 Oct 25;263(2):297-310. PMID:8913308[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang F, Yan Z, Liu Z, Wang S, Wu Q, Yu S, Ding J, Dai Q. Molecular basis of toxicity of N-type calcium channel inhibitor MVIIA. Neuropharmacology. 2016 Feb;101:137-45. PMID:26344359 doi:10.1016/j.neuropharm.2015.08.047
- ↑ Gao S, Yao X, Yan N. Structure of human Ca(v)2.2 channel blocked by the painkiller ziconotide. Nature. 2021 Aug;596(7870):143-147. PMID:34234349 doi:10.1038/s41586-021-03699-6
- ↑ Kim JI, Takahashi M, Ohtake A, Wakamiya A, Sato K. Tyr13 is essential for the activity of omega-conotoxin MVIIA and GVIA, specific N-type calcium channel blockers. Biochem Biophys Res Commun. 1995 Jan 17;206(2):449-54. PMID:7826361 doi:10.1006/bbrc.1995.1063
- ↑ Nielsen KJ, Thomas L, Lewis RJ, Alewood PF, Craik DJ. A consensus structure for omega-conotoxins with different selectivities for voltage-sensitive calcium channel subtypes: comparison of MVIIA, SVIB and SNX-202. J Mol Biol. 1996 Oct 25;263(2):297-310. PMID:8913308 doi:S0022-2836(96)90576-8
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