6Z8C

Crystal Structure of the Voltage-Gated Sodium Channel NavMs (F208L) in complex with N-desmethyltamoxifen (3.2 A resolution)

6Z8C の概要

• エントリーDOI: 10.2210/pdb6z8c/pdb
• 分子名称: Ion transport protein, SODIUM ION, HEGA-10, ... (6 entities in total)
• 機能のキーワード: voltage gated sodium channel, membrane protein, metal transport
• 由来する生物種: Magnetococcus marinus MC-1
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33275.30

構造登録者

Sula, A.,Hollingworth, D.,Wallace, B.A. (登録日: 2020-06-02, 公開日: 2021-02-03, 最終更新日: 2024-01-24)

主引用文献

Sula, A.,Hollingworth, D.,Ng, L.C.T.,Larmore, M.,DeCaen, P.G.,Wallace, B.A.
A tamoxifen receptor within a voltage-gated sodium channel.
Mol.Cell, 81:1160-, 2021

PubMed Abstract: Voltage-gated sodium channels are targets for many analgesic and antiepileptic drugs whose therapeutic mechanisms and binding sites have been well characterized. We describe the identification of a previously unidentified receptor site within the NavMs voltage-gated sodium channel. Tamoxifen, an estrogen receptor modulator, and its primary and secondary metabolic products bind at the intracellular exit of the channel, which is a site that is distinct from other previously characterized sodium channel drug sites. These compounds inhibit NavMs and human sodium channels with similar potencies and prevent sodium conductance by delaying channel recovery from the inactivated state. This study therefore not only describes the structure and pharmacology of a site that could be leveraged for the development of new drugs for the treatment of sodium channelopathies but may also have important implications for off-target health effects of this widely used therapeutic drug.

PubMed: 33503406
DOI: 10.1016/j.molcel.2020.12.048

実験手法

X-RAY DIFFRACTION (3.2 Å)