2h8s
From Proteopedia
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| - | [[Image:2h8s.gif|left|200px]] | ||
| - | + | ==Solution structure of alpha-conotoxin Vc1.1== | |
| - | + | <StructureSection load='2h8s' size='340' side='right'caption='[[2h8s]]' scene=''> | |
| - | | | + | == Structural highlights == |
| - | | | + | <table><tr><td colspan='2'>[[2h8s]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_victoriae Conus victoriae]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H8S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H8S 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=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=2h8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h8s OCA], [https://pdbe.org/2h8s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h8s RCSB], [https://www.ebi.ac.uk/pdbsum/2h8s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h8s ProSAT]</span></td></tr> | |
| - | + | </table> | |
| - | + | == Function == | |
| - | + | [https://www.uniprot.org/uniprot/CA1A_CONVC CA1A_CONVC] Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This synthetic peptide (produced without hydroxyproline, nor 4-carboxyglutamate) is a neuronal nAChR antagonist that acts as a powerful analgesic. It blocks nAChRs composed of alpha-3 or -5/beta-2 (IC(50)=7.2 uM), alpha-3/beta-2 (IC(50)=7.3 uM), alpha-3/beta-4 (IC(50)=4.2 uM), alpha-3 or -5/beta-4 (IC(50)<30 uM), alpha-4/beta-2 (IC(50)<30 uM), alpha-4/beta-4 (IC(50)<30 uM) and alpha/beta/gamma/delta (IC(50)<30 uM) subunits.<ref>PMID:12779345</ref> <ref>PMID:15770155</ref> | |
| - | + | <div style="background-color:#fffaf0;"> | |
| - | + | == Publication Abstract from PubMed == | |
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The alpha-conotoxin Vc1.1 is a small disulfide-bonded peptide currently in development as a treatment for neuropathic pain. This study describes the synthesis, determination of the disulfide connectivity, and the determination of the three-dimensional structure of Vc1.1 using NMR spectroscopy. Vc1.1 was shown to inhibit nicotine-evoked membrane currents in isolated bovine chromaffin cells in a concentration-dependent manner and preferentially targets peripheral nicotinic acetylcholine receptor (nAChR) subtypes over central subtypes. Specifically, Vc1.1 is selective for alpha3-containing nAChR subtypes. The three-dimensional structure of Vc1.1 comprises a small alpha-helix spanning residues Pro6 to Asp11 and is braced by the I-III, II-IV disulfide connectivity seen in other alpha-conotoxins. A comparison of the structure of Vc1.1 with other alpha-conotoxins, taken together with nAChR selectivity data, suggests that the conserved proline at position 6 is important for binding, whereas a number of residues in the C-terminal portion of the peptide contribute toward the selectivity. The structure reported here should open new opportunities for further development of Vc1.1 or analogues as analgesic agents. | The alpha-conotoxin Vc1.1 is a small disulfide-bonded peptide currently in development as a treatment for neuropathic pain. This study describes the synthesis, determination of the disulfide connectivity, and the determination of the three-dimensional structure of Vc1.1 using NMR spectroscopy. Vc1.1 was shown to inhibit nicotine-evoked membrane currents in isolated bovine chromaffin cells in a concentration-dependent manner and preferentially targets peripheral nicotinic acetylcholine receptor (nAChR) subtypes over central subtypes. Specifically, Vc1.1 is selective for alpha3-containing nAChR subtypes. The three-dimensional structure of Vc1.1 comprises a small alpha-helix spanning residues Pro6 to Asp11 and is braced by the I-III, II-IV disulfide connectivity seen in other alpha-conotoxins. A comparison of the structure of Vc1.1 with other alpha-conotoxins, taken together with nAChR selectivity data, suggests that the conserved proline at position 6 is important for binding, whereas a number of residues in the C-terminal portion of the peptide contribute toward the selectivity. The structure reported here should open new opportunities for further development of Vc1.1 or analogues as analgesic agents. | ||
| - | + | The synthesis, structural characterization, and receptor specificity of the alpha-conotoxin Vc1.1.,Clark RJ, Fischer H, Nevin ST, Adams DJ, Craik DJ J Biol Chem. 2006 Aug 11;281(32):23254-63. Epub 2006 Jun 5. PMID:16754662<ref>PMID:16754662</ref> | |
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| - | The synthesis, structural characterization, and receptor specificity of the alpha-conotoxin Vc1.1., Clark RJ, Fischer H, Nevin ST, Adams DJ, Craik DJ | + | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 2h8s" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Conus victoriae]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Adams DJ]] | ||
| + | [[Category: Clark RJ]] | ||
| + | [[Category: Craik DJ]] | ||
| + | [[Category: Fischer H]] | ||
| + | [[Category: Nevin ST]] | ||
Current revision
Solution structure of alpha-conotoxin Vc1.1
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