Allostery in homodimeric SARS-CoV-2 main protease.

ABSTRACT: Many enzymes work as homodimers with two distant catalytic sites, but the reason for this choice is often not clear. For the main protease M^pro of SARS-CoV-2, dimerization is essential for function and plays a regulatory role during the coronaviral replication process. Here, to analyze a possible allosteric mechanism, we use X-ray crystallography, native mass spectrometry, isothermal titration calorimetry, and activity assays to study the interaction of M^pro with three peptide substrates. Crystal structures show how the plasticity of M^pro is exploited to face differences in the sequences of the natural substrates. Importantly, unlike in the free form, the M^pro dimer in complex with these peptides is asymmetric and the structures of the substrates

SUBMITTER: Fornasier E 

PROVIDER: S-EPMC11535432 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature