2h8s
From Proteopedia
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Solution structure of alpha-conotoxin Vc1.1
Overview
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.
About this Structure
2H8S is a Single protein structure of sequence from [1] with as ligand. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 17:39:21 2008
