Fig. 3.

(A) Binding of F901318 to A. fumigatus DHODH. A homology model of A. fumigatus DHODH was created, and the binding mode of F901318 (cyan) was estimated. The product orotate (orange) and the cofactor flavin mononucleotide (FMN; magenta) are also shown. Residues predicted to be close to the molecule are highlighted. (B) F901318 inhibits a mutant version, but not the WT version, of C. albicans DHODH. Recombinant C. albicans DHODH residues Phe₁₆₂ and Val₁₇₁ were mutated to Val and Met, respectively (their predicted equivalents in A. fumigatus DHODH). The IC₅₀ of F901318 inhibition of the WT and mutant DHODH proteins is displayed in the right-hand column (A. fumigatus IC₅₀, n = 11, SD = 0.01 μM; WT C. albicans IC₅₀, n = 7, all seven replicates had an IC₅₀ >90 μM; C. albicans_V162_M171 IC₅₀, n = 7, SD = 0.91 μM).