6LQA

voltage-gated sodium channel Nav1.5 with quinidine

6LQA の概要

• エントリーDOI: 10.2210/pdb6lqa/pdb
• EMDBエントリー: 0942
• 分子名称: Sodium channel protein type 5 subunit alpha, 2-acetamido-2-deoxy-beta-D-glucopyranose, Quinidine (3 entities in total)
• 機能のキーワード: membrane protein, voltage-gated sodium channel, transport protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 234059.23

構造登録者

Yan, N.,Li, Z.,Pan, X.,Huang, G. (登録日: 2020-01-13, 公開日: 2021-03-24, 最終更新日: 2024-11-06)

主引用文献

Li, Z.,Jin, X.,Wu, T.,Huang, G.,Wu, K.,Lei, J.,Pan, X.,Yan, N.
Structural Basis for Pore Blockade of the Human Cardiac Sodium Channel Na v 1.5 by the Antiarrhythmic Drug Quinidine*.
Angew.Chem.Int.Ed.Engl., 60:11474-11480, 2021

PubMed Abstract: Na 1.5, the primary voltage-gated Na (Na ) channel in heart, is a major target for class I antiarrhythmic agents. Here we present the cryo-EM structure of full-length human Na 1.5 bound to quinidine, a class Ia antiarrhythmic drug, at 3.3 Å resolution. Quinidine is positioned right beneath the selectivity filter in the pore domain and coordinated by residues from repeats I, III, and IV. Pore blockade by quinidine is achieved through both direct obstruction of the ion permeation path and induced rotation of an invariant Tyr residue that tightens the intracellular gate. Structural comparison with a truncated rat Na 1.5 in the presence of flecainide, a class Ic agent, reveals distinct binding poses for the two antiarrhythmics within the pore domain. Our work reported here, along with previous studies, reveals the molecular basis for the mechanism of action of class I antiarrhythmic drugs.

PubMed: 33684260
DOI: 10.1002/anie.202102196

実験手法

ELECTRON MICROSCOPY (3.3 Å)