Cooperativity and communication between the active sites of the dimeric SARS-CoV-2 main protease.

ABSTRACT: The coronaviral main protease (M^pro) has been the subject of various biochemical and structural studies and a drug target against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. SARS-CoV-2 M^pro is active as a dimer, but despite apparent cooperativity in catalytic activity, how the two distal active sites communicate and modulate binding and/or catalysis is unclear. Here, we have investigated the interplay between cooperativity, dimerization, and substrate cleavage in SARS-CoV-2 M^pro through a combination of enzymatic assays, crystal structures, and protein characterization. To disentangle the contribution of each active site to the observed enzymatic activity, we developed a cleavage assay involving heterodimers of active and inacti

SUBMITTER: Zvornicanin SN 

PROVIDER: S-EPMC12810614 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature