Fungicidal amphotericin B sponges are assemblies of staggered asymmetric homodimers encasing large void volumes
| العنوان: | Fungicidal amphotericin B sponges are assemblies of staggered asymmetric homodimers encasing large void volumes |
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| المؤلفون: | Agnieszka Lewandowska, Corinne P. Soutar, Alexander I. Greenwood, Evgeny Nimerovsky, Ashley M. De Lio, Jordan T. Holler, Grant S. Hisao, Anuj Khandelwal, Jiabao Zhang, Anna M. SantaMaria, Charles D. Schwieters, Taras V. Pogorelov, Martin D. Burke, Chad M. Rienstra |
| المصدر: | Nat Struct Mol Biol |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Antifungal Agents, Cell Membrane, Molecular Conformation, Molecular Dynamics Simulation, Streptomyces, Article, Immunocompromised Host, Structural Biology, Amphotericin B, Ergosterol, Humans, Nuclear Magnetic Resonance, Biomolecular, Molecular Biology, Cells, Cultured, Invasive Fungal Infections |
| الوصف: | Amphotericin B (AmB) is a powerful but toxic fungicide that operates via enigmatic small molecule–small molecule interactions. This mechanism has challenged the frontiers of structural biology for half a century. We recently showed AmB primarily forms extramembranous aggregates that kill yeast by extracting ergosterol from membranes. Here, we report key structural features of these antifungal ‘sponges’ illuminated by high-resolution magic-angle spinning solid-state NMR, in concert with simulated annealing and molecular dynamics computations. The minimal unit of assembly is an asymmetric head-to-tail homodimer: one molecule adopts an all-trans C1–C13 motif, the other a C6–C7-gauche conformation. These homodimers are staggered in a clathrate-like lattice with large void volumes similar to the size of sterols. These results illuminate the atomistic interactions that underlie fungicidal assemblies of AmB and suggest this natural product may form biologically active clathrates that host sterol guests. |
| تدمد: | 1545-9985 1545-9993 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::79d1354f9972e7ba8e6e7c9d0c9a5c48Test https://doi.org/10.1038/s41594-021-00685-4Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....79d1354f9972e7ba8e6e7c9d0c9a5c48 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15459985 15459993 |
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