Fig. 2: Enfumafungin binding site of Fks1 and Fks2.
From: Inhibition mechanism of the fungal β−1,3-glucan synthases by triterpenoid antifungal drugs
a Molecular formula of enfumafungin. b MIC of enfumafungin for S. cerevisiae. Cell viability assay of yeast in medium containing enfumafungin in a series of concentrations, indicating the MIC of enfumafungin at 0.072 μg/ml. c Cryo-EM maps of Fks1 in complex with enfumafungin (Fks1–EFU). The electron density of enfumafungin is shown as a mesh, and the structure is represented as sticks. d Cryo-EM maps of Fks2 in complex with enfumafungin (Fks2–EFU). The electron density of enfumafungin is shown as a mesh, and the structure is represented as sticks. e Interaction network between EFU and Fks1. Key residues involved in the interaction are shown as sticks. f Interaction network between EFU and Fks2. Key residues involved in the interaction are shown as sticks. g Relative position of the EFU to the active site and glucan transport channel in a model of Fks1–EFU in complex with Rho1 and β-1,3-glucan. Structural coordinates for Rho1 were obtained from PDB 8WLA, and the 1,3-β-glucan product model was derived from PDB 7YUY. The EFU-binding pocket is positioned approximately 30 Å from the catalytic site of Fks1 and roughly 20 Å from the predicted glucan translocation channel. The top panel presents a cartoon and semi-transparent surface representation of the Fks1–EFU structural model. The bottom panel offers a zoom-in view of the EFU-binding site, the active site, and the 1,3-β-glucan chain. h UDP-Glc hydrolysis activity of wild type (WT) and mutant Fks1 with or without enfumafungin. The reaction without Fks1 was used as the control (Ctr). Data points represent the mean ± SD (n = 3). i MIC50 for EFU in wild-type S. cerevisiae cells (Ctl) and fks1Δ cells with a plasmid carrying either wild-type Fks1 (WT) or mutants. Data points represent the mean ± SD (n = 3). Source data are provided as a Source Data file.
