FIG 2.
Analysis of DG167 analogues binding to KasA. (A and B) Cartoon representation of two DG167 molecules (DG167A [green sticks] and DG167B [magenta sticks]) or one molecule of 5g (pink sticks) binding to a KasA dimer with one protomer colored cyan (KasA) and the other colored orange (KasA′). In panel A, the KasA′ residues that interact with DG167 are depicted as orange sticks. These residues are similarly displayed in panel B but make no contacts to the analog 5g. Dashed lines indicate bond distances measured in angstroms. (C to E) MST quantification for DG167, its transposed indazole analogue 5g, and its inactive des-methyl analog 5a-2 binding to KasA. DG167, 5a-2, and 5g were titrated at between 0.007 nM and 100,000 nM with 49.5 nM labeled KasA. DG167 binds to KasA with an EC50 of 130.9 ± 18.2 nM. 5a-2 binds to KasA with an EC50 of 1,736.1 ± 221.2 nM. 5g binds to KasA with a Kd = 46.5 ± 18.7 nM.