Structure-directed antifungal discovery
Location(s): United States
The project will use the first high resolution X-ray structure of a fungal cytochrome P450 enzyme to facilitate structure-directed antifungal discovery. Lanosterol 14α-demethylase catalyses the step in the ergosterol biosynthetic pathway targeted by the triazole antifungal drugs. The project will involve the expression and crystallization of lanosterol 14α-demethylase from clinically important fungal pathogens and its human orthologue CYP51. It will also involve X-ray crystallography of yeast lanosterol 14α-demethylase crystallized with hit compounds identified as lead antifungal candidates. The goals of the research are to more fully understand the mechanism of lanosterol 14α-demethylase and identify new classes of broad-spectrum antifungals.