2M3I

Characterization of a Novel Alpha4/6-Conotoxin TxIC from Conus textile that Potently Blocks alpha3beta4 Nicotinic Acetylcholine Receptors

2M3I の概要

• エントリーDOI: 10.2210/pdb2m3i/pdb
• NMR情報: BMRB: 18964
• 分子名称: Alpha-conotoxin (1 entity in total)
• 機能のキーワード: alpha-conotoxin, alpha-helix, disulfide bonds, amidated c-terminus, toxin
• 由来する生物種: Conus lividus
• 細胞内の位置: Secreted (By similarity): H9N3R7
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1493.82

構造登録者

Luo, S.,Zhangsun, D.,Zhu, X.,Wu, Y.,Hu, Y.,Christensen, S.,Akcan, M.,Craik, D.J.,McIntosh, J.M. (登録日: 2013-01-20, 公開日: 2013-12-04, 最終更新日: 2024-10-16)

主引用文献

Luo, S.,Zhangsun, D.,Zhu, X.,Wu, Y.,Hu, Y.,Christensen, S.,Harvey, P.J.,Akcan, M.,Craik, D.J.,McIntosh, J.M.
Characterization of a Novel alpha-Conotoxin TxID from Conus textile That Potently Blocks Rat alpha 3 beta 4 Nicotinic Acetylcholine Receptors.
J.Med.Chem., 56:9655-9663, 2013

PubMed Abstract: The α3β4 nAChRs are implicated in pain sensation in the PNS and addiction to nicotine in the CNS. We identified an α-4/6-conotoxin (CTx) TxID from Conus textile. The new toxin consists of 15 amino acid residues with two disulfide bonds. TxID was synthesized using solid phase methods, and the synthetic peptide was functionally tested on nAChRs heterologously expressed in Xenopus laevis oocytes. TxID blocked rat α3β4 nAChRs with a 12.5 nM IC50, which places it among the most potent α3β4 nAChR antagonists. TxID also blocked the closely related α6/α3β4 with a 94 nM IC50 but showed little activity on other nAChR subtypes. NMR analysis showed that two major structural isomers exist in solution, one of which adopts a regular α-CTx fold but with different surface charge distribution to other 4/6 family members. α-CTx TxID is a novel tool with which to probe the structure and function of α3β4 nAChRs.

PubMed: 24200193
DOI: 10.1021/jm401254c

実験手法

SOLUTION NMR