Amphotericin B assembles into seven-molecule ion channels: An NMR and molecular dynamics study
Year: 2022
Type: article
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 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.
Source: Science Advances
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
Awards: G2712646973, Dynamic conformation and domain structure of lipid molecules in model biomembranes, Protein function control starting from the pharmacophore skeleton of natural products for the development of new bioactive compounds, Establishment of research base for lipid chemical biology, Challenges to create natural product-drug conjugate starting from screening of natural products that bind to membrane proteins, G5462346855, Chemical study on dynamics of model lipid bilayers reproducing biomembrane under non-equilibrium conditions, 村田脂質活性構造プロジェクト
OpenAlex ID: W4283018830