7N89

Room-temperature X-ray structure of SARS-CoV-2 main protease C145A mutant in complex with substrate Ac-SAVLQSGF-CONH2

Summary for 7N89

• Entry DOI: 10.2210/pdb7n89/pdb
• Descriptor: 3C-like proteinase, ACE-SER-ALA-VAL-LEU-GLN-SER-GLY-PHE-NH2 (3 entities in total)
• Functional Keywords: cysteine protease, c145a mutant, homodimer, hydrolase
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 4
• Total formula weight: 69250.83

Authors

Kovalevsky, A.,Kneller, D.W.,Coates, L. (deposition date: 2021-06-14, release date: 2021-06-23, Last modification date: 2024-11-13)

Primary citation

Kneller, D.W.,Zhang, Q.,Coates, L.,Louis, J.M.,Kovalevsky, A.
Michaelis-like complex of SARS-CoV-2 main protease visualized by room-temperature X-ray crystallography.
Iucrj, 8:973-979, 2021

PubMed Abstract: SARS-CoV-2 emerged at the end of 2019 to cause an unprecedented pandemic of the deadly respiratory disease COVID-19 that continues to date. The viral main protease (M) is essential for SARS-CoV-2 replication and is therefore an important drug target. Understanding the catalytic mechanism of M, a cysteine protease with a catalytic site comprising the noncanonical Cys145-His41 dyad, can help in guiding drug design. Here, a 2.0 Å resolution room-temperature X-ray crystal structure is reported of a Michaelis-like complex of M harboring a single inactivating mutation C145A bound to the octapeptide Ac-SAVLQSGF-CONH corresponding to the nsp4/nsp5 autocleavage site. The peptide substrate is unambiguously defined in subsites S5 to S3' by strong electron density. Superposition of the Michaelis-like complex with the neutron structure of substrate-free M demonstrates that the catalytic site is inherently pre-organized for catalysis prior to substrate binding. Induced fit to the substrate is driven by P1 Gln binding in the predetermined subsite S1 and rearrangement of subsite S2 to accommodate P2 Leu. The Michaelis-like complex structure is ideal for modeling of the SARS-CoV-2 M catalytic mechanism.

PubMed: 34804549
DOI: 10.1107/S2052252521010113

Experimental method

X-RAY DIFFRACTION (2 Å)