7CN0

Cryo-EM structure of K+-bound hERG channel

7CN0 の概要

• エントリーDOI: 10.2210/pdb7cn0/pdb
• EMDBエントリー: 30412
• 分子名称: potassium channel 1, POTASSIUM ION (2 entities in total)
• 機能のキーワード: potassium channel, transport protein
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 367246.54

構造登録者

Asai, T.,Adachi, N.,Moriya, T.,Kawasaki, M.,Suzuki, K.,Senda, T.,Murata, T. (登録日: 2020-07-29, 公開日: 2021-01-20, 最終更新日: 2024-03-27)

主引用文献

Asai, T.,Adachi, N.,Moriya, T.,Oki, H.,Maru, T.,Kawasaki, M.,Suzuki, K.,Chen, S.,Ishii, R.,Yonemori, K.,Igaki, S.,Yasuda, S.,Ogasawara, S.,Senda, T.,Murata, T.
Cryo-EM Structure of K + -Bound hERG Channel Complexed with the Blocker Astemizole.
Structure, 29:203-212.e4, 2021

PubMed Abstract: The hERG channel is a voltage-gated potassium channel involved in cardiac repolarization. Off-target hERG inhibition by drugs has become a critical issue in the pharmaceutical industry. The three-dimensional structure of the hERG channel was recently reported at 3.8-Å resolution using cryogenic electron microscopy (cryo-EM). However, the drug inhibition mechanism remains unclear because of the scarce structural information regarding the drug- and potassium-bound hERG channels. In this study, we obtained the cryo-EM density map of potassium-bound hERG channel complexed with astemizole, a well-known hERG inhibitor that increases risk of potentially fatal arrhythmia, at 3.5-Å resolution. The structure suggested that astemizole inhibits potassium conduction by binding directly below the selectivity filter. Furthermore, we propose a possible binding model of astemizole to the hERG channel and provide insights into the unusual sensitivity of hERG to several drugs.

PubMed: 33450182
DOI: 10.1016/j.str.2020.12.007

実験手法

ELECTRON MICROSCOPY (3.9 Å)