9EH4

Solution structure of alpha conotoxin LvID

9EH4 の概要

• エントリーDOI: 10.2210/pdb9eh4/pdb
• NMR情報: BMRB: 31219
• 分子名称: Alpha conotoxin LvID (1 entity in total)
• 機能のキーワード: conotoxin, toxin
• 由来する生物種: Conus lividus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1748.01

構造登録者

Harvey, P.J.,Craik, D.J. (登録日: 2024-11-22, 公開日: 2025-04-23, 最終更新日: 2025-05-07)

主引用文献

Guo, M.,Zhu, X.,Ma, T.,Xu, C.,Zhangsun, D.,Yu, J.,Kaas, Q.,Harvey, P.J.,McIntosh, J.M.,Craik, D.J.,Luo, S.
Selective Inhibition of Rat alpha 7 Nicotinic Acetylcholine Receptors by LvID, a Newly Characterized alpha 4/7-Conotoxin from Conus lividus .
J.Med.Chem., 68:8163-8173, 2025

PubMed Abstract: The α7 nicotinic acetylcholine receptors (nAChRs), identified in peripheral and central nervous systems, are crucial for cognitive function, memory, inflammation, and are linked to disorders like Alzheimer's disease (AD), lung cancer, myasthenia gravis, and atherosclerosis. Here we report that a novel α4/7-conotoxin (CTx) LvID, from , potently inhibits rat α7 nAChRs expressed in oocytes with an IC of 13.8 nM, showing little activity against other rat nAChR subtypes. The structure of LvID was elucidated using nuclear magnetic resonance (NMR) spectroscopy and comprises a short helix braced by disulfide bonds. The key residues of LvID that bind to the α7 nAChRs were determined from a series of alanine mutants. Molecular simulation provided a possible explanation for the activity and specificity of LvID binding to α7 nAChRs. This finding offers a vital pharmacological tool for investigating the structural features and functional mechanisms of α7 nAChRs.

PubMed: 40205658
DOI: 10.1021/acs.jmedchem.4c02810

実験手法

SOLUTION NMR