Fig. 2: Mpro L50F/E166A/L167F triple mutant crystal structure showing L50F mutation at the protein-protein interface.
From: Distal protein-protein interactions contribute to nirmatrelvir resistance
a Mpro triple mutant dimer of a dimer (dark green/green, magenta/salmon), showing P1–P6 residues (magenta stick) of the C-terminus from the substrate dimer (post cleavage, a.k.a, product) bound in the active site of the enzyme dimer (green). Zoomed-in view shows the interactions of the enzyme F50 (green) within the substrate hydrophobic pocket (magenta). Substrate residues are noted in red text. b Close-up view of the binding pose of P1–P6 bound in the triple mutant active site (substrate shown in magenta and enzyme shown in green). The N-terminus from an adjacent protomer is noted in orange. Substrate residues are noted in red text. c Movement of the 166–168 backbone in the triple mutant with P1–P6 bound in the active site (magenta/green) vs. Mpro C145A with nsp5/6 substrate bound (cyan/light purple) (PDB 7MB5). Substrate residues are noted in red text, and the N-terminus from an adjacent monomer is noted in orange. d Binding pose of nirmatrelvir (white, PBD 8DCZ) superimposed into the triple mutant binding pocket. The N-terminus from an adjacent protomer is noted in orange.
