Figure 3

Homology model of R. arrhizus LDM F5. (A) Superimposition showing the active site of R. arrhizus LDM F5 (green) showing the position of F129 in relation to S. cerevisiae Y140 (purple, PDB ID: 5HS1)43. Voriconazole (green carbons, blue nitrogens, red oxygens and cyan fluorines) is shown coordinating to the heme (orange) in the homology model. The key water-mediated hydrogen bonding network centered on the water molecule (red sphere) with hydrogen bonds is shown by dashed lines. The orange dashed line shows the hydrogen bond that is lost in the presence of phenylalanine (F129) substitution compared with tyrosine (Y140). The water molecule is present only in the crystal structure. (B) Substitution of serine (S. cerevisiae S382) for asparagine (R. arrhizus LDM F5 N362) can be seen adjacent to VCZ and shows no polar interactions. This is highlighted by the superimposition of the homology model (green) onto the crystal structure (purple). The water molecule is present only in the crystal structure.