2021年3月
Cryo-EM Structure of K+-Bound hERG Channel Complexed with the Blocker Astemizole
Structure
- 巻
- 29
- 号
- 3
- 開始ページ
- 203
- 終了ページ
- 212.e4
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.str.2020.12.007
- 出版者・発行元
- Elsevier BV
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.
- リンク情報
- ID情報
-
- DOI : 10.1016/j.str.2020.12.007
- ISSN : 0969-2126
- PubMed ID : 33450182