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| | ==SOLUTION STRUCTURE OF OMEGA-CONOTOXIN GVIA USING 2-D NMR SPECTROSCOPY AND RELAXATION MATRIX ANALYSIS== | | ==SOLUTION STRUCTURE OF OMEGA-CONOTOXIN GVIA USING 2-D NMR SPECTROSCOPY AND RELAXATION MATRIX ANALYSIS== |
| - | <StructureSection load='1omc' size='340' side='right'caption='[[1omc]], [[NMR_Ensembles_of_Models | 21 NMR models]]' scene=''> | + | <StructureSection load='1omc' size='340' side='right'caption='[[1omc]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1omc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Conge Conge]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OMC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OMC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1omc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_geographus Conus geographus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OMC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OMC FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene>, <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, 21 models</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1omc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1omc OCA], [http://pdbe.org/1omc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1omc RCSB], [http://www.ebi.ac.uk/pdbsum/1omc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1omc ProSAT]</span></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=1omc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1omc OCA], [https://pdbe.org/1omc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1omc RCSB], [https://www.ebi.ac.uk/pdbsum/1omc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1omc ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CO16A_CONGE CO16A_CONGE]] Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels (Cav). | + | [https://www.uniprot.org/uniprot/O16A_CONGE O16A_CONGE] Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels (Cav). This toxin blocks N-type calcium channels (Cav2.2/CACNA1B) with a high potency (it displaces [125I]GVIA with an IC(50)=3.7-38 pM) (PubMed:10938268, PubMed:11724570).<ref>PMID:10938268</ref> <ref>PMID:11724570</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: Conge]] | + | [[Category: Conus geographus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Basus, V J]] | + | [[Category: Basus VJ]] |
| - | [[Category: Bradley, E K]] | + | [[Category: Bradley EK]] |
| - | [[Category: Davis, J H]] | + | [[Category: Davis JH]] |
| - | [[Category: Miljanich, G P]] | + | [[Category: Miljanich GP]] |
| - | [[Category: Nadasdi, L]] | + | [[Category: Nadasdi L]] |
| - | [[Category: Ramachandran, J]] | + | [[Category: Ramachandran J]] |
| - | [[Category: Presynaptic neurotoxin]]
| + | |
| Structural highlights
Function
O16A_CONGE Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels (Cav). This toxin blocks N-type calcium channels (Cav2.2/CACNA1B) with a high potency (it displaces [125I]GVIA with an IC(50)=3.7-38 pM) (PubMed:10938268, PubMed:11724570).[1] [2]
Publication Abstract from PubMed
We report here the solution structure of omega-conotoxin GVIA, a peptide antagonist of the N-type neuronal voltage-sensitive calcium channel. The structure was determined using two-dimensional NMR in combination with distance geometry and restrained molecular dynamics. The full relaxation matrix analysis program MARDIGRAS was used to generate maximum and minimum distance restraints from the crosspeak intensities in NOESY spectra. The 187 restraints obtained were used in conjunction with 23 angle restraints from vicinal coupling constants as input for the structure calculations. The backbones of the best 21 structures match with an average pairwise RMSD of 0.58 A. The structures contain a short segment of triple-stranded beta-sheet involving residues 6-8, 18-21, and 24-27, making this the smallest published peptide structure to contain a triple-stranded beta-sheet. Conotoxins have been shown to be effective neuroprotective agents in animal models of brain ischemia. Our results should aid in the design of novel nonpeptide compounds with potential therapeutic utility.
Solution structure of omega-conotoxin GVIA using 2-D NMR spectroscopy and relaxation matrix analysis.,Davis JH, Bradley EK, Miljanich GP, Nadasdi L, Ramachandran J, Basus VJ Biochemistry. 1993 Jul 27;32(29):7396-405. PMID:8338837[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
- ↑ Favreau P, Gilles N, Lamthanh H, Bournaud R, Shimahara T, Bouet F, Laboute P, Letourneux Y, Ménez A, Molgó J, Le Gall F. A new omega-conotoxin that targets N-type voltage-sensitive calcium channels with unusual specificity. Biochemistry. 2001 Dec 4;40(48):14567-75. PMID:11724570 doi:10.1021/bi002871r
- ↑ Davis JH, Bradley EK, Miljanich GP, Nadasdi L, Ramachandran J, Basus VJ. Solution structure of omega-conotoxin GVIA using 2-D NMR spectroscopy and relaxation matrix analysis. Biochemistry. 1993 Jul 27;32(29):7396-405. PMID:8338837
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