Michaelis-like complex of SARS-CoV-2 main protease visualized by room-temperature X-ray crystallography.

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^pro) is essential for SARS-CoV-2 replication and is therefore an important drug target. Understanding the catalytic mechanism of M^pro, 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^pro harboring a single inactivating mutation C145A bound to the octapeptide Ac-SAVLQSGF-CONH₂ corresponding to the nsp4/nsp5 autocleavage site. The peptide substrate is unambiguously defined in subsites S5 to S3' by strong

SUBMITTER: Kneller DW 

PROVIDER: S-EPMC8562657 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature