Fungicidal amphotericin B sponges are assemblies of staggered asymmetric homodimers encasing large void volumes.

ABSTRACT: 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 th

SUBMITTER: Lewandowska A 

PROVIDER: S-EPMC9336184 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature