Figure 3
Structure of the MuPEP1–Compound 2 Complex and the Compound 2-binding Site. (A) The crystal structure of the tMuPEP1–Compound 2 complex and an |F o |−|F c | omit map. The electron density is shown around the compound and contoured at a level of 2.5 σ (blue mesh). The side chains of the catalytic triad residues, Cys17 (yellow), His96 (blue), and Asp112 (red), are shown as sticks. The oxygen and nitrogen of Compound 2 are colored red and blue, respectively. (B) Superimposition of the structures of the free tMuPEP1 (cyan) and the tMuPEP1-Compound 2 complex (white). The residues that interact with Compound 2 are shown as sticks and are labeled. The oxygen and nitrogen of Compound 2 are colored red and blue, respectively. (C) Surface representation of the result of the HotPatch program performed on MuPEP133. The hydrophobic region is colored blue, and the hydrophilic region is red. The hydrophobic concave surface that is the binding site for the N-terminal helix of ComC is encircled by an orange line, and the inhibitor binding pocket is encircled by a magenta line. (D) Amino acid sequence alignment of PEPs from different species of Streptococcus ComA and the peptidase domain of S. pneumoniae BlpA. The completely identical amino acid residues and the partially identical amino acid residues (at least four out of seven sequences) among PEP sequences are shaded black and gray, respectively. MuPEP1, S. mutans PEP; PPEP, S. pneumoniae PEP; MiPEP, S. mitis PEP; OPEP, S. oralis PEP; CPEP, S. cristatus PEP; GPEP, S. gordonii PEP; and BlpAPEP, the peptidase domain of S. pneumoniae BlpA. Dots indicate 13 amino acid residues that are in close contact with Compound 2 in the structure of the tMuPEP1-Compound 2 complex.
