7UJ9

Room-temperature X-ray structure of monomeric SARS-CoV-2 main protease catalytic domain (MPro1-199)

Summary for 7UJ9

• Entry DOI: 10.2210/pdb7uj9/pdb
• Descriptor: 3C-like proteinase nsp5 (2 entities in total)
• Functional Keywords: cysteine protease, catalytic domain, viral enzyme, hydrolase
• Biological source: Severe acute respiratory syndrome coronavirus 2
• Total number of polymer chains: 2
• Total formula weight: 45956.27

Authors

Kovalevsky, A.,Kneller, D.W.,Coates, L. (deposition date: 2022-03-30, release date: 2022-10-05, Last modification date: 2023-10-18)

Primary citation

Nashed, N.T.,Kneller, D.W.,Coates, L.,Ghirlando, R.,Aniana, A.,Kovalevsky, A.,Louis, J.M.
Autoprocessing and oxyanion loop reorganization upon GC373 and nirmatrelvir binding of monomeric SARS-CoV-2 main protease catalytic domain.
Commun Biol, 5:976-976, 2022

PubMed Abstract: The monomeric catalytic domain (residues 1-199) of SARS-CoV-2 main protease (MPro) fused to 25 amino acids of its flanking nsp4 region mediates its autoprocessing at the nsp4-MPro junction. We report the catalytic activity and the dissociation constants of MPro and its analogs with the covalent inhibitors GC373 and nirmatrelvir (NMV), and the estimated monomer-dimer equilibrium constants of these complexes. Mass spectrometry indicates the presence of the accumulated adduct of NMV bound to MPro and MPro and not of GC373. A room temperature crystal structure reveals a native-like fold of the catalytic domain with an unwound oxyanion loop (E state). In contrast, the structure of a covalent complex of the catalytic domain-GC373 or NMV shows an oxyanion loop conformation (E* state) resembling the full-length mature dimer. These results suggest that the E-E* equilibrium modulates autoprocessing of the main protease when converting from a monomeric polyprotein precursor to the mature dimer.

PubMed: 36114420
DOI: 10.1038/s42003-022-03910-y

Experimental method

X-RAY DIFFRACTION (2.25 Å)