Amphotericin B assembles into seven-molecule ion channels: An NMR and molecular dynamics study

Yuichi Umegawa, Tomoya Yamamoto, Mayank Dixit, Kosuke Funahashi, Sangjae Seo, Yasuo Nakagawa, Taiga Suzuki, Shigeru Matsuoka, Hiroshi Tsuchikawa, Shinya Hanashima, Tohru Oishi, Nobuaki Matsumori, Wataru Shinoda, Michio Murata

研究成果: ジャーナルへの寄稿学術誌査読

抄録

Amphotericin B, an antifungal drug with a long history of use, forms fungicidal ion-permeable channels across cell membranes. Using solid-state nuclear magnetic resonance spectroscopy and molecular dynamics simulations, we experimentally elucidated the three-dimensional structure of the molecular assemblies formed by this drug in membranes in the presence of the fungal sterol ergosterol. A stable assembly consisting of seven drug molecules was observed to form an ion conductive channel. The structure is somewhat similar to the upper half of the barrel-stave model proposed in the 1970s but substantially different in the number of molecules and in their arrangement. The present structure explains many previous findings, including structure-activity relationships of the drug, which will be useful for improving drug efficacy and reducing adverse effects.

本文言語英語
論文番号eabo2658
ジャーナルScience Advances
8
24
DOI
出版ステータス出版済み - 6月 2022

!!!All Science Journal Classification (ASJC) codes

  • 一般

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