Structural and functional insights into Ubl domain-mediated regulation of SARS-CoV-2 PLpro.

ABSTRACT:

Background

SARS-CoV-2 papain-like protease (PLpro) is essential for viral replication and immune evasion. It contains an N-terminal ubiquitin-like (Ubl) domain, whose involvement in enzymatic function remains poorly understood.

Results

In this study, we investigated the role of the Ubl domain in modulating the structural dynamics and catalytic efficiency of PLpro. Using molecular dynamics (MD) simulations, inhibitor binding assays, and steady-state kinetic analyses, we found that the Ubl domain stabilizes critical structural elements, notably the ridge helix in the thumb subdomain. Removal of the Ubl domain altered substrate processing, reducing catalytic efficiency of the enzyme. Interestingly, free ubiquitin enhanced enzymatic activity, likely via non-canonical binding sit

SUBMITTER: Arya R 

PROVIDER: S-EPMC12495856 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature