Papain-like protease

Papain-like proteases (or papain-like (cysteine) peptidases; abbreviated PLP or PLCP) are a large family of cysteine protease enzymes that share structural and enzymatic properties with the group's namesake member, papain. They are found in all domains of life. In animals, the group is commonly referred to as cysteine cathepsins or, in older literature, lysosomal peptidases. In the MEROPS protease enzyme classification system, papain-like proteases belong to Clan CA. These proteases share a common catalytic dyad active site featuring a cysteine amino acid residue that functions as a nucleophile.

The human genome encodes eleven cysteine cathepsins, which perform a broad range of physiological functions. In some parasites, papain-like proteases play roles in host invasion, such as cruzipain from Trypanosoma cruzi. In plants, they are involved in host defense and developmental processes. Studies of papain-like proteases in prokaryotes have lagged behind those of eukaryotic counterparts. In cellular organisms, papain-like proteases are synthesized as inactive preproenzymes and become enzymatically active only after maturation. Their activity is tightly regulated, often by endogenous protease inhibitors such as cystatins. In many RNA viruses, including important human pathogens such as the coronaviruses SARS-CoV and SARS-CoV-2, papain-like protease protein domains are involved in processing viral polyproteins into mature nonstructural proteins. Consequently, many papain-like proteases are considered potential drug targets.