Structural and mechanistic insights into fungal β-1,3-glucan synthase FKS1.

ABSTRACT: The membrane-integrated synthase FKS is involved in the biosynthesis of β-1,3-glucan, the core component of the fungal cell wall^1,2. FKS is the target of widely prescribed antifungal drugs, including echinocandin and ibrexafungerp^3,4. Unfortunately, the mechanism of action of FKS remains enigmatic and this has hampered development of more effective medicines targeting the enzyme. Here we present the cryo-electron microscopy structures of Saccharomyces cerevisiae FKS1 and the echinocandin-resistant mutant FKS1(S643P). These structures reveal the active site of the enzyme at the membrane-cytoplasm interface and a glucan translocation path spanning the membrane bilayer. Multiple bound lipids and notable membrane distortions are observed in the FKS1 structures, suggesting

SUBMITTER: Hu X 

PROVIDER: S-EPMC10032269 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature