4CBC

Open-form NavMS Sodium Channel Pore (with C-terminal Domain) after thallium soak

4CBC の概要

• エントリーDOI: 10.2210/pdb4cbc/pdb
• 関連するPDBエントリー: 4CAL 4CBD
• 分子名称: ION TRANSPORT PROTEIN, HEGA-10, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: transport protein, sodium channel, selectivity filter, membrane protein
• 由来する生物種: MAGNETOCOCCUS MARINUS MC-1
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 69760.88

構造登録者

Bagneris, C.,Naylor, C.E.,Wallace, B.A. (登録日: 2013-10-12, 公開日: 2014-05-28, 最終更新日: 2023-12-20)

主引用文献

Bagneris, C.,Decaen, P.G.,Naylor, C.E.,Pryde, D.C.,Nobeli, I.,Clapham, D.E.,Wallace, B.A.
Prokaryotic Navms Channel as a Structural and Functional Model for Eukaryotic Sodium Channel Antagonism.
Proc.Natl.Acad.Sci.USA, 111:8428-, 2014

PubMed Abstract: Voltage-gated sodium channels are important targets for the development of pharmaceutical drugs, because mutations in different human sodium channel isoforms have causal relationships with a range of neurological and cardiovascular diseases. In this study, functional electrophysiological studies show that the prokaryotic sodium channel from Magnetococcus marinus (NavMs) binds and is inhibited by eukaryotic sodium channel blockers in a manner similar to the human Nav1.1 channel, despite millions of years of divergent evolution between the two types of channels. Crystal complexes of the NavMs pore with several brominated blocker compounds depict a common antagonist binding site in the cavity, adjacent to lipid-facing fenestrations proposed to be the portals for drug entry. In silico docking studies indicate the full extent of the blocker binding site, and electrophysiology studies of NavMs channels with mutations at adjacent residues validate the location. These results suggest that the NavMs channel can be a valuable tool for screening and rational design of human drugs.

PubMed: 24850863
DOI: 10.1073/PNAS.1406855111

実験手法

X-RAY DIFFRACTION (2.664 Å)