2H8S

Solution structure of alpha-conotoxin Vc1.1

2H8S の概要

• エントリーDOI: 10.2210/pdb2h8s/pdb
• NMR情報: BMRB: 7177
• 分子名称: Alpha-conotoxin Vc1A (1 entity in total)
• 機能のキーワード: alpha-conotoxin, alpha-helix, disulfide bonds, amidated c-terminus, toxin
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1812.02

構造登録者

Clark, R.J.,Fischer, H.,Nevin, S.T.,Adams, D.J.,Craik, D.J. (登録日: 2006-06-07, 公開日: 2006-06-27, 最終更新日: 2024-10-09)

主引用文献

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

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: 16754662
DOI: 10.1074/jbc.M604550200

実験手法

SOLUTION NMR