FIG. 2.

RAB1 occupies a similar space as the natural substrate and other inhibitors; in addition it utilizes a unique surface cavity. The IC₅₀ of RAB1 is not affected by the F98Y mutation to the same extent as other inhibitors. RAB1 is depicted as yellow in the binding site (blue), residue 98 is marked with a red surface, and the listed small molecules are superimposed. (A) RAB1 with IC₅₀ data from the current study. (B) BAL0030543, a related compound under development against S. aureus, with IC₅₀ data from reference 7. (C) Dihydrofolic acid, with coordinates obtained from PDB ID 3FRD (26) (D) Trimethoprim, with IC₅₀ data from the current study and the coordinates obtained from PDB ID 2W9G with NADPH (22). (E) Iclaprim, with IC₅₀ and coordinates obtained from PDB IDs 3FYV and 3FYW (27). (F) Propargyl-based inhibitors, with IC₅₀ data and coordinates obtained from PDB ID 3F0B (19) and from PDB ID 3F0Q (K. M. Frey et al., unpublished; no IC₅₀ data are publicly available).