Fig. 2: Long-range structural changes correlated with C117-C145 disulfide formation disrupt the dimer interface.
From: SARS-CoV-2 Mpro responds to oxidation by forming disulfide and NOS/SONOS bonds
A aligned overlay of reduced (orange: monoclinic/room temperature, PDB ID: 7PXZ; yellow: orthorhombic/100 K, PDB ID: 7Z2K) and oxidized (cyan: orthorhombic/room temperature, PDB ID: 7PZQ) structures, with one monomer of the Mpro dimer shown as surface. Oxidation of the active site cysteine, C145, results in B disulfide bridge formation with C117 and displacement of N28 (density: oxidized 2mFo-DFc at 1 RMSD). Colocalization of C117 and C145 requires C displacement of C-terminal residues 301–306 from the dimer interface and is correlated with D a shift of the dimerization domain and disruption of the stabilizing interactions between the two protomers. E MSA showing N28, C117, and C145 are conserved across related coronaviruses. N28 and C145 are absolutely conserved in the set studied. C117 is partially conserved, but where it is not, another cysteine is present in either position 116 or 142 (magenta) that could conceivably fulfill the same role.
