Fig. 6. Characterization of wild-type Mpro C12 acyl-enzyme complex structure and comparison to wild-type C12 product complex and C5 acyl-enzyme complex.
a mFo-DFc omit electron density map (contoured at 3.0 σ, blue mesh) shows the thioester bond between the mainchain carbonyl carbon of Gln306 (chain C; residues Leu305 and Gln306 shown) and the Sγ of Cys145 within the wild type Mpro catalytic site (chain B; His41 and Cys145 shown) of C12. The ball-and-stick structure is shown with carbon green, nitrogen blue, sulfur gold, and oxygen red. b Analysis of the C12 acyl-enzyme structure (chains B and C). Ball-and-stick (carbon green, nitrogen blue, oxygen red, sulfur gold) view shows the geometry and atomic interactions of the thioester bond between the Sγ of Cys145 and main chain carbonyl carbon of Gln306. The trigonal planar thioester group, defined by atoms Cα, C, and O of Gln306, and Sγ of Cys145 is shown as is the χ1 dihedral angle (defined by atoms N, Cα, Cβ, and Sγ). The oxyanion hole hydrogen bond distances and angles are shown. c Analogous analysis of the acyl-enzyme intermediate of C5 (chain B and symmetry-related chain B) with ball-and-stick view shown (carbon light blue, nitrogen blue, oxygen red, sulfur gold). The proposed deacylating water is shown as a cyan sphere. d Superposition of the C12 WT acyl-enzyme complex (green carbons, chains B and C) and C5 WT acyl-enzyme complex (light blue carbons, chain B, and symmetry-related chain B) complexes. e Superposition of the C12 WT acyl-enzyme complex (green carbons, chains B and C) and the C12 WT product complex (magenta carbons, chains D and E). f Superposition of the C12 C145A product complex (cyan carbons, chains B and C) and the C12 WT product complex (magenta carbons, chains D and E).