6YZ2

Full length Open-form Sodium Channel NavMs F208L

6YZ2 の概要

• エントリーDOI: 10.2210/pdb6yz2/pdb
• 分子名称: Ion transport protein, SODIUM ION, HEGA-10, ... (5 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 (strain ATCC BAA-1437 / JCM 17883 / MC-1)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33596.57

構造登録者

Sula, A.,Sait, L.G.,Hollingworth, D.,Wallace, B.A. (登録日: 2020-05-06, 公開日: 2020-11-11, 最終更新日: 2024-01-24)

主引用文献

Sait, L.G.,Sula, A.,Ghovanloo, M.R.,Hollingworth, D.,Ruben, P.C.,Wallace, B.A.
Cannabidiol interactions with voltage-gated sodium channels.
Elife, 9:-, 2020

PubMed Abstract: Voltage-gated sodium channels are targets for a range of pharmaceutical drugs developed for the treatment of neurological diseases. Cannabidiol (CBD), the non-psychoactive compound isolated from cannabis plants, was recently approved for treatment of two types of epilepsy associated with sodium channel mutations. This study used high-resolution X-ray crystallography to demonstrate the detailed nature of the interactions between CBD and the NavMs voltage-gated sodium channel, and electrophysiology to show the functional effects of binding CBD to these channels. CBD binds at a novel site at the interface of the fenestrations and the central hydrophobic cavity of the channel. Binding at this site blocks the transmembrane-spanning sodium ion translocation pathway, providing a molecular mechanism for channel inhibition. Modelling studies suggest why the closely-related psychoactive compound tetrahydrocannabinol may not have the same effects on these channels. Finally, comparisons are made with the TRPV2 channel, also recently proposed as a target site for CBD. In summary, this study provides novel insight into a possible mechanism for CBD interactions with sodium channels.

PubMed: 33089780
DOI: 10.7554/eLife.58593

実験手法

X-RAY DIFFRACTION (2.2 Å)