2H8S
Solution structure of alpha-conotoxin Vc1.1
Summary for 2H8S
| Entry DOI | 10.2210/pdb2h8s/pdb |
| NMR Information | BMRB: 7177 |
| Descriptor | Alpha-conotoxin Vc1A (1 entity in total) |
| Functional Keywords | alpha-conotoxin, alpha-helix, disulfide bonds, amidated c-terminus, toxin |
| Total number of polymer chains | 1 |
| Total formula weight | 1812.02 |
| Authors | Clark, R.J.,Fischer, H.,Nevin, S.T.,Adams, D.J.,Craik, D.J. (deposition date: 2006-06-07, release date: 2006-06-27, Last modification date: 2024-10-09) |
| Primary citation | Clark, R.J.,Fischer, H.,Nevin, S.T.,Adams, D.J.,Craik, D.J. The Synthesis, Structural Characterization, and Receptor Specificity of the {alpha}-Conotoxin Vc1.1. J.Biol.Chem., 281:23254-23263, 2006 Cited by PubMed Abstract: 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. PubMed: 16754662DOI: 10.1074/jbc.M604550200 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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