Any feedback?
Information on EC 3.4.22.B50 - papain-like proteinase 2
for references in articles please use BRENDA:EC3.4.22.B50preliminary BRENDA-supplied EC number
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
3.4.22.B50 papain-like proteinase 2Specify your search results
Word Map
- 3.4.22.B50
- polyproteins
-
replicase
- coronaviruses
- 3clpro
- isg15
-
3c-like
-
mhv-a59
- nsp3
- coronaviral
- pp1ab
- medicine
- drug development
The enzyme appears in viruses and cellular organisms
Reaction Schemes
responsible for the cleavages located at the N-terminus of the replicase polyprotein
Synonyms
sars-cov plpro, papain-like proteinase, papain-like cysteine proteinase, plp-2, pl2pro, ervatamin-c, erv-c, papain-like protease domain 2, 
more
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
mouse hepatitis virus papain-like proteinase 2
-
-
-
-
papain-like protease
papain-like protease domain 2
-
a catalytic domain of the nonstructural protein 3 of mouse hepatitis virus A59
papain-like proteinase
PL2-PRO
-
-
-
-
PLP-2
-
-
-
-
PLP2
PLpro
SARS-coronavirus papain-like protease
-
-
severe acute respiratory syndrome coronavirus papain-like protease
-
PLP2
-
-
-
-
PLP2
-
papain-like protease core domain 2 is part of non-structural protein 3
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
responsible for the cleavages located at the N-terminus of the replicase polyprotein
-
-
-
-
responsible for the cleavages located at the N-terminus of the replicase polyprotein
catalytic cycle and proposed chemical mechanism of the SARS-coronavirus papain-like protease catalyzed reaction, of the catalytic triad residues Cys112 acts as nucleophile, His273 functions as a general acid-base, and Asp287 is paired with histidine helping to align it and promote deprotonation of Cys112, structure-function relationship, overview
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CAS REGISTRY NUMBER
COMMENTARY
851883-30-2
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
Dabcyl-FRLKGGAPIKGV-Edans + H2O
?
SARS-CoV-derived substrate
-
-
?
FRLKGG-4-nitroanilide + H2O
FRLKGG + 4-nitroaniline
-
-
-
?
N-benzoyl-Phe-Val-Arg-4-nitroanilide + H2O
N-benzoyl-Phe-Val-Arg + 4-nitroaniline
-
-
-
?
polyubiquitin + H2O
monoubiquitin + ?
the enzyme cleaves Lys48- and Lys63-linked polyubiquitin to monoubiquitin but not linear polyubiquitin
-
-
?
RELNGGAVTRYV + H2O
AVTYRV + RELNGG
-
12 mer oligopeptide containing Gly180-Ala181, 5% cleavage
-
-
?
replicase polyprotein + H2O
?
-
PLP2 cleaves a substrate encoding the first predicted membrane-spanning domain, MP1, of the replicase polyprotein. Processing the replicase polyprotein at this site generates the p150 replicase intermediate that is likely critical for embedding the replicase complex into cellular membranes. The enzyme acts efficiently in trans
-
-
?
RLRGG-7-amido-4-methylcoumarin + H2O
RLRGG + 7-amino-4-methylcoumarin
-
-
-
?
ubiquitin-7-amido-4-trifluoro-methyl-coumarin + H2O
ubiquitin + 7-amino-4-trifluoro-methyl-coumarin
-
-
-
?
ubiquitin-7-amido-4-trifluoromethylcoumarin + H2O
ubiquitin + 7-amino-4-trifluoromethylcoumarin
the enzyme catalyzes proteolytic processing of the viral polyprotein and also shows significant in vitro deubiquitinating and de-ISGylating activities. The enzyme binds ubiquitin, the ubiquitin core makes mostly hydrophilic interactions with the enzyme, while the Leu-Arg-Gly-Gly C-terminus of ubiquitin is located in the catalytic cleft of the enzyme. The ubiquitin core binds to the palm, thumb and fingers domains of the enzyme, while its final four C-terminal residues bind into a narrow channel by a network of hydrogen bonds and reach towards the active site
-
-
?
ubiquitinated RIG-I + H2O
deubiquitinated RIG-I + ubiquitin
-
-
-
?
ubiquitinated STING + H2O
deubiquitinated STING + ubiquitin
-
-
-
?
viral replicase polyprotein + H2O
?
-
PLP2 is responsible for processing both cleavage sites 2 and 3 to release nsp2 and nsp3. The cleavage sites are identified as FTKLAG-/-GKISFS for CS2 and VAKQGA-/-GFKRTY for CS3.
-
-
?
Z-KKAG-7-amido-4-methylcoumarin + H2O
Z-KKAG + 7-amino-4-methylcoumarin
the catalytic efficiency toward Z-KKAG-7-amido-4-methylcoumarin is 5times higher than that for Z-LRGG-7-amido-4-methylcoumarin
-
-
?
Z-LRGG-7-amido-4-methylcoumarin + H2O
Z-LRGG + 7-amino-4-methylcoumarin
-
-
-
?
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine + H2O
?
-
fluorogenic substrate
-
-
?
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine + H2O
?
-
fluorogenic substrate
-
-
?
FRLKGGAPIKGV
?
-
12 mer oligopeptide containing Gly818-Ala819, 100% cleavage
-
-
?
FRLKGGAPIKGV
?
-
12 mer oligopeptide containing Gly818-Ala819, 100% cleavage
-
-
?
ISLKGGKIVSTC
?
-
12 mer oligopeptide containing Gly2740-Lys2741, 29% cleavage
-
-
?
ISLKGGKIVSTC
?
-
12 mer oligopeptide containing Gly2740-Lys2741, 29% cleavage
-
-
?
ubiquitin + H2O
?
-
the enzyme cleaves the LRGG tail of ubiquitin
-
-
?
ubiquitin + H2O
?
the enzyme processes both K-48 and K-63 linked polyubiquitin chains
-
-
?
additional information
?
-
-
SARS-CoV PLP2 does not cleave HCoV.229E and IBV substrates
-
-
?
additional information
?
-
-
SARS-CoV PLP2 does not cleave HCoV.229E and IBV substrates
-
-
?
additional information
?
-
-
proteolytic processing of the human coronavirus 229E. PL2pro is able to cleave the nsp1-nsp2 cleavage site. PL2pro plays a universal and essential proteolytic role that appears to be assisted by the PL1pro paralog at specific sites
-
-
?
additional information
?
-
-
the core domain of PLP2 has in vivo deubiquitinase and DeISGylation activity
-
-
?
additional information
?
-
the enzyme cannot cleave Z-KAGG-7-amido-4-methylcoumarin
-
-
?
additional information
?
-
-
no in vitro cleavage of the ORF 1a polyprotein in cis or in trans can be detected with PLP-2 expressed either as a polypeptide, including flanking viral sequences, or as an MBP fusion protein
-
-
?
additional information
?
-
-
the enzyme is one of three distinct viral proteases (PLP1, PLP2 and 3CLpro) involved in processing of the replicase polyprotein
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
polyubiquitin + H2O
monoubiquitin + ?
the enzyme cleaves Lys48- and Lys63-linked polyubiquitin to monoubiquitin but not linear polyubiquitin
-
-
?
replicase polyprotein + H2O
?
-
PLP2 cleaves a substrate encoding the first predicted membrane-spanning domain, MP1, of the replicase polyprotein. Processing the replicase polyprotein at this site generates the p150 replicase intermediate that is likely critical for embedding the replicase complex into cellular membranes. The enzyme acts efficiently in trans
-
-
?
ubiquitinated RIG-I + H2O
deubiquitinated RIG-I + ubiquitin
-
-
-
?
ubiquitinated STING + H2O
deubiquitinated STING + ubiquitin
-
-
-
?
additional information
?
-
-
the enzyme is one of three distinct viral proteases (PLP1, PLP2 and 3CLpro) involved in processing of the replicase polyprotein
-
-
?
ubiquitin + H2O
?
-
the enzyme cleaves the LRGG tail of ubiquitin
-
-
?
ubiquitin + H2O
?
the enzyme processes both K-48 and K-63 linked polyubiquitin chains
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
-
the fingers domain of the enzyme contains a zinc ion that is tetrahedrally coordinated by four cysteines
additional information
-
no effect by Mg2+, Ca2+, Mn2+, Co2+, and Ni2+
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(4E)-1,7-bis(3,4-dihydroxyphenyl)hept-4-en-3-one
-
a natural diarylheptanoide inhibitor
(7R)-5,7-dihydroxy-8-(4-hydroxy-3-methoxyphenyl)-2-(4-hydroxy-4-methylpentyl)-2-methyl-3,4,7,8-tetrahydro-2H,6H-pyrano[3,2-g]chromen-6-one
-
a natural geranylated flavonoid inhibitor
1,6,6-trimethyl-1,2,6,7,8,9-hexahydrophenanthro[1,2-b]furan-10,11-dione
-
a natural tanshinone inhibitor
2-methyl-N-[(1R)-1-(naphthalen-2-yl)ethyl]benzamide
-
over 90% inhibition at 0.1 mM
2-methyl-N-[(1S)-1-(naphthalen-2-yl)ethyl]benzamide
-
14% inhibition at 0.1 mM
2-methyl-N-[1-(naphthalen-2-yl)ethyl]benzamide
-
racemat
5-amino-2-methyl-N-[(1R)-1-(naphthalen-1-yl)ethyl]benzamide
-
R-isomer, a potent, noncovalent, competitive inhibitor
N-(1,3-benzodioxol-5-ylmethyl)-1-[(1R)-1-(naphthalen-1-yl)ethyl]piperidine-4-carboxamide
-
-
N-(3-fluorobenzyl)-1-[(1R)-1-(naphthalen-1-yl)ethyl]piperidine-4-carboxamide
-
-
N-(4-fluorobenzyl)-1-[(1R)-1-(naphthalen-1-yl)ethyl]piperidine-4-carboxamide
-
-
N-(4-methoxybenzyl)-1-(naphthalen-1-ylmethyl)piperidine-4-carboxamide
-
-
N-cyclohexyl-2-aminethanesulfonic acid
the molecule binds near the catalytic triad
N-ethyl-N-phenyldithiocarbamic acid-Zn(II)
-
-
-
N-[(2-methoxypyridin-4-yl)methyl]-1-[(1R)-1-(naphthalen-1-yl)ethyl]piperidine-4-carboxamide
-
-
N-[3-(acetylamino)benzyl]-1-[(1R)-1-(naphthalen-1-yl)ethyl]piperidine-4-carboxamide
-
-
Ub-3Br
suicide inhibitor, i.e. ubiquitin(1-75)-3-bromopropylamide
-
6-Mercaptopurine
competitive and reversible inhibitor
6-thioguanine
competitive and reversible inhibitor
additional information
-
not inhibited by Mg2+, Mn2+, Ca2+, Ni2+ and Co2+ at 0.01 mM, E64, leupeptin and antipain at 0.1 mM, N-ethylmaleimide and chymostatin at 1 mM and cystatin at 0.01 mg/mL respectively
-
additional information
-
not sensitive to cysteine protease inhibitor E-64d
-
additional information
-
not sensitive to cysteine protease inhibitor E64d
-
additional information
-
enzyme structure, function and inhibition by designed antiviral compounds, overview. No inhibition by NSC158362. Selectivity of naphthalene-based enzyme inhibitors, overview
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Bone Resorption
Different cysteine proteinases involved in bone resorption and osteoclast formation.
Bronchitis
Characterization of the two overlapping papain-like proteinase domains encoded in gene 1 of the coronavirus infectious bronchitis virus and determination of the C-terminal cleavage site of an 87-kDa protein.
Bronchitis
Identification of a novel cleavage activity of the first papain-like proteinase domain encoded by open reading frame 1a of the coronavirus Avian infectious bronchitis virus and characterization of the cleavage products.
Carcinoma, Squamous Cell
Crystal structure of SCCA1 and insight about the interaction with JNK1.
Coronavirus Infections
Inhibitor recognition specificity of MERS-CoV papain-like protease may differ from that of SARS-CoV.
COVID-19
Structure-based drug designing of naphthalene based SARS-CoV PLpro inhibitors for the treatment of COVID-19.
Drug-Related Side Effects and Adverse Reactions
Nanoparticles of ZnO/Berberine complex contract COVID-19 and respiratory co-bacterial infection in addition to elimination of hydroxychloroquine toxicity.
Foot-and-Mouth Disease
Foot-and-mouth disease virus leader proteinase: a papain-like enzyme requiring an acidic environment in the active site.
Foot-and-Mouth Disease
Multifunctional roles of leader protein of foot-and-mouth disease viruses in suppressing host antiviral responses.
Foot-and-Mouth Disease
Recognition of eukaryotic initiation factor 4G isoforms by picornaviral proteinases.
Foot-and-Mouth Disease
The Leader Proteinase of Foot-and-Mouth Disease Virus Negatively Regulates the Type I Interferon Pathway by Acting as a Viral Deubiquitinase.
Hepatitis
Characterization of a second cleavage site and demonstration of activity in trans by the papain-like proteinase of the murine coronavirus mouse hepatitis virus strain A59.
Hepatitis
Replication of murine hepatitis virus is regulated by papain-like proteinase 1 processing of nonstructural proteins 1, 2, and 3.
Hepatitis
The autocatalytic release of a putative RNA virus transcription factor from its polyprotein precursor involves two paralogous papain-like proteases that cleave the same peptide bond.
Mouth Diseases
Recognition of eukaryotic initiation factor 4G isoforms by picornaviral proteinases.
Retinoblastoma
Inhibitory activity of a heterochromatin-associated serpin (MENT) against papain-like cysteine proteinases affects chromatin structure and blocks cell proliferation.
Severe Acute Respiratory Syndrome
Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity.
Severe Acute Respiratory Syndrome
Structure-Based Screening to Discover New Inhibitors for Papain-like Proteinase of SARS-CoV-2: An In Silico Study.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3.23
Z-KKAG-7-amido-4-methylcoumarin
in 20 mM Tris-HCl, pH 7.5, 0.1 mg/ml BSA, 150 mM NaCl, 2 mM dithiothreitol, at 25°C
0.67
Z-LRGG-7-amido-4-methylcoumarin
in 20 mM Tris-HCl, pH 7.5, 0.1 mg/ml BSA, 150 mM NaCl, 2 mM dithiothreitol, at 25°C
0.0396
Dabcyl-FKKKGGGDVKE-Edans
mutant T39W, pH 6.5, 30°C
0.0616
Dabcyl-FKKKGGGDVKE-Edans
wild-type, pH 6.5, 30°C
0.0186
Dabcyl-FRLKGGAPIKGV-Edans
wild-type, pH 6.5, 30°C
0.0321
Dabcyl-FRLKGGAPIKGV-Edans
mutant T39W, pH 6.5, 30°C
0.09687
N-benzoyl-Phe-Val-Arg-4-nitroanilide
mutant enzyme S32T/A67Y, in 50 mM Na-acetate buffer pH 5.0, at 60°C
0.1273
N-benzoyl-Phe-Val-Arg-4-nitroanilide
wild type enzyme, in 50 mM Na-acetate buffer pH 5.0, at 60°C
0.1499
N-benzoyl-Phe-Val-Arg-4-nitroanilide
mutant enzyme S32T, in 50 mM Na-acetate buffer pH 5.0, at 60°C
0.1769
N-benzoyl-Phe-Val-Arg-4-nitroanilide
mutant enzyme A67Y, in 50 mM Na-acetate buffer pH 5.0, at 60°C
0.73
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant wild-type enzyme, pH 7.4, 30°C
-
1.01
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant mutant E168R, pH 7.4, 30°C
-
1.1
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant mutant E168D, pH 7.4, 30°C
-
1.2
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant mutant L163Q, pH 7.4, 30°C
-
1.26
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant mutant E168A, pH 7.4, 30°C
-
1.35
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant mutant Y265F, pH 7.4, 30°C
-
2.48
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant mutant Y265A, pH 7.4, 30°C
-
3.33
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant mutant D165A, pH 7.4, 30°C
-
additional information
additional information
Michaelis-Menten steady-state enzyme-kinetics of wild-type and mutant enzymes, overview
-
additional information
additional information
-
Michaelis-Menten steady-state enzyme-kinetics of wild-type and mutant enzymes, overview
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0041
Dabcyl-FKKKGGGDVKE-Edans
mutant T39W, pH 6.5, 30°C
0.005
Dabcyl-FKKKGGGDVKE-Edans
wild-type, pH 6.5, 30°C
0.0011
Dabcyl-FRLKGGAPIKGV-Edans
wild-type, pH 6.5, 30°C
0.0175
Dabcyl-FRLKGGAPIKGV-Edans
mutant T39W, pH 6.5, 30°C
0.23
N-benzoyl-Phe-Val-Arg-4-nitroanilide
wild type enzyme, in 50 mM Na-acetate buffer pH 5.0, at 60°C
1.43
N-benzoyl-Phe-Val-Arg-4-nitroanilide
mutant enzyme S32T/A67Y, in 50 mM Na-acetate buffer pH 5.0, at 60°C
2.23
N-benzoyl-Phe-Val-Arg-4-nitroanilide
mutant enzyme S32T, in 50 mM Na-acetate buffer pH 5.0, at 60°C
2.65
N-benzoyl-Phe-Val-Arg-4-nitroanilide
mutant enzyme A67Y, in 50 mM Na-acetate buffer pH 5.0, at 60°C
0.01
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant mutant Y265A, pH 7.4, 30°C
-
0.04
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant mutant D165A, pH 7.4, 30°C
-
0.09
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant mutant L163Q, pH 7.4, 30°C
-
0.29
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant mutant E168A, pH 7.4, 30°C
-
0.36
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant mutant E168R, pH 7.4, 30°C
-
0.61
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant mutant E168D, pH 7.4, 30°C
-
0.61
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant mutant Y265F, pH 7.4, 30°C
-
0.79
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant wild-type enzyme, pH 7.4, 30°C
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.082
Dabcyl-FKKKGGGDVKE-Edans
wild-type, pH 6.5, 30°C
0.103
Dabcyl-FKKKGGGDVKE-Edans
mutant T39W, pH 6.5, 30°C
0.055
Dabcyl-FRLKGGAPIKGV-Edans
mutant T39W, pH 6.5, 30°C
0.058
Dabcyl-FRLKGGAPIKGV-Edans
wild-type, pH 6.5, 30°C
1.8
N-benzoyl-Phe-Val-Arg-4-nitroanilide
wild type enzyme, in 50 mM Na-acetate buffer pH 5.0, at 60°C
14.75
N-benzoyl-Phe-Val-Arg-4-nitroanilide
mutant enzyme A67Y, in 50 mM Na-acetate buffer pH 5.0, at 60°C
14.76
N-benzoyl-Phe-Val-Arg-4-nitroanilide
mutant enzyme S32T/A67Y, in 50 mM Na-acetate buffer pH 5.0, at 60°C
14.87
N-benzoyl-Phe-Val-Arg-4-nitroanilide
mutant enzyme S32T, in 50 mM Na-acetate buffer pH 5.0, at 60°C
0.045
RLRGG-7-amido-4-methylcoumarin
wild type enzyme, at pH 8.0 and 37°C
0.065
RLRGG-7-amido-4-methylcoumarin
mutant enzyme I353R, at pH 8.0 and 37°C
0.155
RLRGG-7-amido-4-methylcoumarin
mutant enzyme I353W, at pH 8.0 and 37°C
0.01
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant mutant Y265A, pH 7.4, 30°C
-
0.08
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant mutant D165A, pH 7.4, 30°C
-
0.23
ubiquitin-7-amido-4-trifluoromethylcoumarin