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| | ==SOLUTION STRUCTURE OF OMEGA-CONOTOXIN MVIIC, A HIGH AFFINITY OF P-TYPE CALCIUM CHANNELS, USING 1H NMR SPECTROSCOPY AND COMPLETE RELAXATION MATRIX ANALYSIS== | | ==SOLUTION STRUCTURE OF OMEGA-CONOTOXIN MVIIC, A HIGH AFFINITY OF P-TYPE CALCIUM CHANNELS, USING 1H NMR SPECTROSCOPY AND COMPLETE RELAXATION MATRIX ANALYSIS== |
| - | <StructureSection load='1omn' size='340' side='right'caption='[[1omn]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> | + | <StructureSection load='1omn' size='340' side='right'caption='[[1omn]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[1omn]] 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=1OMN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OMN FirstGlance]. <br> | | <table><tr><td colspan='2'>[[1omn]] 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=1OMN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OMN 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, 15 models</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=1omn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1omn OCA], [https://pdbe.org/1omn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1omn RCSB], [https://www.ebi.ac.uk/pdbsum/1omn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1omn 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=1omn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1omn OCA], [https://pdbe.org/1omn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1omn RCSB], [https://www.ebi.ac.uk/pdbsum/1omn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1omn ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CO7C_CONMA CO7C_CONMA]] Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels (Cav). This toxin preferentially blocks P/Q-type calcium channels (Cav2.1/CACNA1A).<ref>PMID:1352986</ref>
| + | [https://www.uniprot.org/uniprot/O17C_CONMA O17C_CONMA] Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels (Cav). This toxin preferentially blocks P/Q-type calcium channels (Cav2.1/CACNA1A) (IC(50)=0.60 nM) (PubMed:10938268, PubMed:1352986). Shows also an inhibition on Cav2.2/CACNA1A channels (IC(50)=7.0 nM) (PubMed:10938268).<ref>PMID:10938268</ref> <ref>PMID:1352986</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | [[Category: Conus magus]] | | [[Category: Conus magus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Basus, V J]] | + | [[Category: Basus VJ]] |
| - | [[Category: Farr-Jones, S]] | + | [[Category: Farr-Jones S]] |
| - | [[Category: Conotoxin]]
| + | |
| - | [[Category: Conus venom]]
| + | |
| - | [[Category: Neurotoxin]]
| + | |
| - | [[Category: P-type calcium channel blocker]]
| + | |
| - | [[Category: Presynaptic neurotoxin]]
| + | |
| Structural highlights
Function
O17C_CONMA Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels (Cav). This toxin preferentially blocks P/Q-type calcium channels (Cav2.1/CACNA1A) (IC(50)=0.60 nM) (PubMed:10938268, PubMed:1352986). Shows also an inhibition on Cav2.2/CACNA1A channels (IC(50)=7.0 nM) (PubMed:10938268).[1] [2]
Publication Abstract from PubMed
We have determined the solution structure of the omega-conotoxin MVIIC from Conus magus by 1H NMR. This conopeptide preferentially blocks P and Q type Ca2+ currents by binding with high affinity to voltage-sensitive Ca2+ channels in neurons. This 26 residue peptide with three disulfide bonds was chemically synthesized and refolded for NMR structural studies. The 1H NMR NOESY spectrum of this peptide was completely assigned, with stereospecific assignments made for 12 of the beta prochiral centers. Complete relaxation matrix analysis using MARDIGRAS was used to obtain initial interproton distances from peak intensities. The correlation time necessary for these calculations was determined by measuring 13C relaxation times using inversely detected natural abundance spectra. Distances were input to DG, which provided 15 starting structures which were then subjected to restrained molecular dynamics calculations using SANDER with the AMBER 91 force field in vacuo. 1H-1H vicinal coupling constants were obtained using a combination of line fitting of both E. COSY and NOESY spectra and used to generate angle restraints that were included explicitly in the restrained molecular dynamics calculations. The final set of the 15 best structures had a backbone rmsd of 0.84 A. The ensemble R1/6 factor calculated by CORMA for the final 15 structures was 11%. The final structure consists of an anti-parallel, triple-stranded beta-sheet, with four turns. In spite of significant differences in amino acid sequence and affinities for calcium channel subtypes, the backbone structure of omega-conotoxin MVIIC is very similar to the previously reported structure of omega-conotoxin GVIA.
Solution structure of omega-conotoxin MVIIC, a high affinity ligand of P-type calcium channels, using 1H NMR spectroscopy and complete relaxation matrix analysis.,Farr-Jones S, Miljanich GP, Nadasdi L, Ramachandran J, Basus VJ J Mol Biol. 1995 Apr 21;248(1):106-24. PMID:7731037[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lewis RJ, Nielsen KJ, Craik DJ, Loughnan ML, Adams DA, Sharpe IA, Luchian T, Adams DJ, Bond T, Thomas L, Jones A, Matheson JL, Drinkwater R, Andrews PR, Alewood PF. Novel omega-conotoxins from Conus catus discriminate among neuronal calcium channel subtypes. J Biol Chem. 2000 Nov 10;275(45):35335-44. PMID:10938268 doi:10.1074/jbc.M002252200
- ↑ Hillyard DR, Monje VD, Mintz IM, Bean BP, Nadasdi L, Ramachandran J, Miljanich G, Azimi-Zoonooz A, McIntosh JM, Cruz LJ, et al.. A new Conus peptide ligand for mammalian presynaptic Ca2+ channels. Neuron. 1992 Jul;9(1):69-77. PMID:1352986
- ↑ Farr-Jones S, Miljanich GP, Nadasdi L, Ramachandran J, Basus VJ. Solution structure of omega-conotoxin MVIIC, a high affinity ligand of P-type calcium channels, using 1H NMR spectroscopy and complete relaxation matrix analysis. J Mol Biol. 1995 Apr 21;248(1):106-24. PMID:7731037 doi:http://dx.doi.org/S0022-2836(85)70205-7
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