Fig. 1: Structure-based design of Pgp3 inhibitors.
From: Structure-based inhibitor design for reshaping bacterial morphology
a Schematic diagram of peptidoglycan structure and domain architecture of Pgp3. Cleavage sites by Pgp3 are shown with scissors. b Surface representation of the electrostatic potential of Pgp3 in complex with tetra-tripeptide and pentapeptide (PDB ID: 6JN0 and 6JN1, respectively). Tetra-tripeptide and pentapeptide are shown in green and orange sticks, respectively. Representative motifs are shown in dashed circles. Substrate binding pocket (S1’, S1, and S2) are colored in lime. c Chemical structure of truncated pentapeptide (mDAP3-D-Ala4-D-Ala5). Green, red, purple, and cyan circles indicate the Y–Y binding motif, hydrophobic pocket binding motif, Zn binding motif, and linker motif, respectively. Substrate-specific binding residues (P1’, P1, and P2) and substrate binding pockets (S1’, S1, and S2) are colored in orange and lime, respectively. d Chemical structure of synthesized inhibitors. BMK-S101 was designed in keeping of Zn binding motif, linker motif, and Y–Y binding motif based on pentapeptide. In BMK-S201, additional binding in hydrophobic pocket was introduced, whereas the rigidity was modulated in BMK-S301 by inserting the linker motif.
