Anti-Ubiquitin polyclonal antibody

Post-translational modifications (PTMs) are crucial for the adaptation of various signalling pathways to ensure cellular homeostasis and proper adaptation to stress. PTM is a covalent addition of a small chemical functional group such as a phosphate group (phosphorylation), methyl group (methylation), or acetyl group (acetylation); lipids like hydrophobic isoprene polymers (isoprenylation); sugars such as a glycosyl group (glycosylation); or even small peptides such as ubiquitin (ubiquitination), SUMO (SUMOylation), NEDD8 (neddylation), etc. SUMO modification changes the function and/or fate of the protein especially under stress conditions, and the consequences of this conjugation can be appreciated from development to diverse disease processes. The impact of SUMOylation in disease has not been monotonous, rather SUMO is found playing a role on both sides of the coin either facilitating or impeding disease progression. Several recent studies have implicated SUMO proteins as key regulators in various cardiovascular disorders. The focus of this review is thus to summarize the current knowledge on the role of the SUMO family in the pathophysiology of cardiovascular diseases.

Viral papain-like cysteine protease (PLpro, NSP3) is essential for SARS-CoV-2 replication and represents a promising target for the development of antiviral drugs. Here, we used a combinatorial substrate library and performed comprehensive activity profiling of SARS-CoV-2 PLpro. On the scaffold of the best hits from positional scanning, we designed optimal fluorogenic substrates and irreversible inhibitors with a high degree of selectivity for SARS PLpro. We determined crystal structures of two of these inhibitors in complex with SARS-CoV-2 PLpro that reveals their inhibitory mechanisms and provides a molecular basis for the observed substrate specificity profiles. Last, we demonstrate that SARS-CoV-2 PLpro harbors deISGylating activity similar to SARSCoV-1 PLpro but its ability to hydrolyze K48-linked Ub chains is diminished, which our sequence and structure analysis provides a basis for. Together, this work has revealed the molecular rules governing PLpro substrate specificity and provides a framework for development of inhibitors with potential therapeutic value or drug repurposing.