Papain-like protease

Papain, the family's namesake member, from Carica papaya
Identifiers
SymbolPeptidase_CA
Pfam clanCL0125
ECOD219.1.1
MEROPSCA

Papain-like proteases (or papain-like (cysteine) peptidases; abbreviated PLP or PLCP) are a large protein 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 often known as cysteine cathepsins or, in older literature, lysosomal peptidases.[1] In the MEROPS protease enzyme classification system, papain-like proteases form Clan CA.[2] Papain-like proteases share a common catalytic dyad active site featuring a cysteine amino acid residue that acts as a nucleophile.[1]

The human genome encodes eleven cysteine cathepsins which have a broad range of physiological functions.[3] In some parasites papain-like proteases have roles in host invasion, such as cruzipain from Trypanosoma cruzi.[1] In plants, they are involved in host defense and in development.[4] Studies of papain-like proteases from prokaryotes have lagged their eukaryotic counterparts.[1] In cellular organisms they are synthesized as preproenzymes that are not enzymatically active until mature, and their activities are tightly regulated, often by the presence of endogenous protease inhibitors such as cystatins.[3] In many RNA viruses, including significant human pathogens such as the coronaviruses SARS-CoV and SARS-CoV-2, papain-like protease protein domains often have roles in processing of polyproteins into mature viral nonstructural proteins.[5][6] Many papain-like proteases are considered potential drug targets.[3][7]

  1. ^ a b c d Novinec M, Lenarčič B (June 2013). "Papain-like peptidases: structure, function, and evolution". Biomolecular Concepts. 4 (3): 287–308. doi:10.1515/bmc-2012-0054. PMID 25436581. S2CID 2112616.
  2. ^ "Summary for clan CA". MEROPS. Retrieved 20 December 2021.
  3. ^ a b c Turk V, Stoka V, Vasiljeva O, Renko M, Sun T, Turk B, et al. (January 2012). "Cysteine cathepsins: from structure, function and regulation to new frontiers". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1824 (1): 68–88. doi:10.1016/j.bbapap.2011.10.002. PMC 7105208. PMID 22024571.
  4. ^ Liu H, Hu M, Wang Q, Cheng L, Zhang Z (4 December 2018). "Role of Papain-Like Cysteine Proteases in Plant Development". Frontiers in Plant Science. 9: 1717. doi:10.3389/fpls.2018.01717. PMC 6288466. PMID 30564252.
  5. ^ Mielech AM, Chen Y, Mesecar AD, Baker SC (December 2014). "Nidovirus papain-like proteases: multifunctional enzymes with protease, deubiquitinating and deISGylating activities". Virus Research. 194: 184–190. doi:10.1016/j.virusres.2014.01.025. PMC 4125544. PMID 24512893.
  6. ^ Hartenian E, Nandakumar D, Lari A, Ly M, Tucker JM, Glaunsinger BA (September 2020). "The molecular virology of coronaviruses". The Journal of Biological Chemistry. 295 (37): 12910–12934. doi:10.1074/jbc.REV120.013930. PMC 7489918. PMID 32661197.
  7. ^ Klemm T, Ebert G, Calleja DJ, Allison CC, Richardson LW, Bernardini JP, et al. (September 2020). "Mechanism and inhibition of the papain-like protease, PLpro, of SARS-CoV-2". The EMBO Journal. 39 (18): e106275. doi:10.15252/embj.2020106275. PMC 7461020. PMID 32845033. S2CID 221328909.