pfam08715: CoV_peptidase (This model is not part of the current CDD release)
Coronavirus papain-like peptidase
This entry contains coronavirus cysteine endopeptidases that belong to MEROPS peptidase family C16 and are required for proteolytic processing of the replicase polyprotein. All coronaviruses encode between one and two accessory cysteine proteinases that recognise and process one or two sites in the amino-terminal half of the replicase polyprotein during assembly of the viral replication complex. HCoV and TGEV encode two accessory proteinases, called coronavirus papain-like proteinase 1 and 2 (PL1-PRO and PL2-PRO). IBV and SARS encodes only one called PL-PRO. They also function as deubiquitinating and deISG15ylating (interferon-induced gene 15) enzymes, disrupting host viral immune response to facilitate viral proliferation and replication. Therefore, this is an important target to develop antiviral treatments. The peptidase family C16 domain is about 260 amino acids in length and structures revealed that it adopts a fold similar that of de-ubiquitinating enzymes. Structures from SARS-CoV-2 determined that it consists of thumb, palm, and fingers subdomains. The thumb is comprised of six alpha-helices and a small beta-hairpin; the fingers subdomain is made of six beta-strands and two alpha-helices and includes a zinc binding site, in which the zinc ion is coordinated by four cysteine residues. Zinc binding is essential for structural integrity and protease activity, with a conformation that varies most between different PL-PRO structures. The palm subdomain is comprised of six beta-strands and includes the catalytic residues Cys-His-Asp, located at the interface between the thumb and palm subdomains.
Jiyao W et al.(2023). "The conserved domain database in 2023.",