Fig. 5: Potential inhibitory mechanisms of JT71.

The apo- and holo-MrkH structures are shown in (a, b), respectively (PDB ID: 5KEC and 5KGO⁵⁵). The N- and C-terminal PilZ domains are indicated. b The two intercalated molecules of c-di-GMP bound to the holo-MrkH are depicted as yellow sticks, and the putative DNA binding groove is labelled. c Overlay of the N-terminal PilZ-like domain of apo- and holo-MrkH illustrating the large domain movement (~138°) that occurs upon binding the two molecules of c-di-GMP to the C-terminal PilZ domain. The root mean square deviation for the overlay of the apo and holo N-terminal PilZ-like domains (Cα atoms) is 0.4 Å. d–f In apo-MrkH, JT71 (green sticks) can bind to a pocket located between the N- and C-terminal PilZ domains. g–i In holo-MrkH, the DNA binding groove is the likely site of interaction of JT71 (magenta sticks). The two molecules of c-di-GMP form part of the putative DNA-binding groove and the JT71 binding pocket. e, h Show the same view as (d, g), respectively, with MrkH and c-di-GMP depicted as molecular surfaces. f, i Close-up view of the two proposed JT71 binding pockets shown in (d, g), nearby residues are shown as sticks. Polar interactions are depicted as black dashed lines. f H62 can interact with the phenyl ring of JT71 via a π-π interaction, whereas in i F114 makes this interaction with JT71.