Papain-like protease

Source: Wikipedia, the free encyclopedia.
Carica papaya
Identifiers
SymbolPeptidase_CA
Pfam clanCL0125
MEROPSCA

Papain-like proteases (or papain-like (cysteine) peptidases; abbreviated PLP or PLCP) are a large

amino acid residue that acts as a nucleophile.[1]

The

drug targets.[3][7]

Classification

The MEROPS system of protease enzyme classification defines clan CA as containing the papain-like proteases. They are thought to have a shared evolutionary origin. As of 2021, the clan contained 45 families.[2][8]

Structure

disulfide bond is shown in cyan. From PDB: 9PAP​.[9]

The structure of papain was among the earliest

enzyme substrate interacts with both domains in an extended conformation.[1][3]

Papain-like proteases are often

propeptide which functions as an inhibitor blocking access to the active site. The propeptide is removed by proteolysis to form the mature enzyme.[1][3][11]

Catalytic mechanism

Papain-like proteases have a

deubiquitinases.[5]

Function

Eukaryotes

Mammals

In animals, especially in mammalian biology, members of the papain-like protease family are usually referred to as cysteine cathepsins - that is, the

V, X, and W. Most cathepsins are expressed throughout the body, but some have narrower tissue distribution.[1][3]

covalent inhibitor odanacatib, shown in light blue with the covalently modified catalytic cysteine in green. Odanacatib was studied in clinical trials as a cathepsin K inhibitor for osteoporosis.[12]

Although historically known as

drug target for osteoporosis.[15]

Parasites

A number of

Chagas' disease.[17]

Plants

X-ray crystallography structure of papain in complex with a cystatin protease inhibitor (orange) from the taro plant. The active site residues are highlighted (cysteine in green and histidine in blue). From PDB: 3IMA​.[18]

Members of the papain-like protease family play a number of important roles in

pathogens.[4] The relationship between plant papain-like proteases and pathogen responses - such as cystatin inhibitors - have been described as an evolutionary arms race.[19]

Some PLP family members in plants have culinary and commercial applications. The family's namesake member,

ficin from figs.[1][20]

Prokaryotes

Although papain-like proteases are found in all

Clostridium difficile;[22] and Lpg2622 from Legionella pneumophila.[23]

Viruses

X-ray crystallography structure of the papain-like protease (PLPro) domain from SARS-CoV-2 non-structural protein 3. The catalytic residues are highlighted with cysteine in green and histidine in blue. The blue sphere is a bound zinc ion. From PDB: 6WZU​.[24]

The papain-like protease family includes a number of

drug target for the development of antiviral drugs.[6][7]

References

  1. ^
    S2CID 2112616
    .
  2. ^ a b c d e "Summary for clan CA". MEROPS. Retrieved 20 December 2021.
  3. ^
    PMID 22024571
    .
  4. ^
    PMID 30564252
    .
  5. ^
    PMID 24512893
    .
  6. ^
    PMID 32661197
    .
  7. ^
    S2CID 221328909
    .
  8. PMID 29145643
    .
  9. ^
    PMID 6502713
    .
  10. S2CID 4169127
    .
  11. ^
    PMID 26157794
    .
  12. PMID 28049758
    .
  13. PMID 30897858
    .
  14. PMID 31555270
    .
  15. PMID 28651365
    .
  16. PMID 15358255
    .
  17. PMID 25994861
    .
  18. PMID 21416241
    .
  19. PMID 27488095
    .
  20. ^
    hdl:11323/1609
    .
  21. S2CID 1367730
    .
  22. PMID 25004975
    .
  23. S2CID 51906615
    .
  24. PMID 33531496
    .
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