1. Amphotericin B assembles into seven-molecule ion channels: An NMR and molecular dynamics study
- Author
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Michio Murata, Hiroshi Tsuchikawa, Shinya Hanashima, Tohru Oishi, Sangjae Seo, Tomoya Yamamoto, Kosuke Funahashi, Taiga Suzuki, Shigeru Matsuoka, Nobuaki Matsumori, Mayank Kumar Dixit, Yuichi Umegawa, Yasuo Nakagawa, and Wataru Shinoda
- Subjects
Ergosterol ,chemistry.chemical_compound ,Molecular dynamics ,Membrane ,Multidisciplinary ,Solid-state nuclear magnetic resonance ,Chemistry ,Antifungal drug ,Biophysics ,Molecule ,Nuclear magnetic resonance spectroscopy ,Ion channel - Abstract
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 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 high-resolution structure explains many previous findings, including structure-activity relationships of the drug, which will be useful for improving drug efficacy and reducing adverse effects.
- Published
- 2022