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(E-EDANS)RELNGGAPI(K-DABCYL)S + H2O
?
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine + H2O
?
azocasein + H2O
?
-
-
-
?
branched polyubiquitin chains + H2O
?
Dabcyl-FKKKGGGDVKE-Edans + H2O
?
-
-
-
?
Dabcyl-FRLKGGAPIKGV-Edans + H2O
?
SARS-CoV-derived substrate
-
-
?
FRLKGG-4-nitroanilide + H2O
FRLKGG + 4-nitroaniline
-
-
-
?
FTKLAGGKISFS + H2O
FTKLAG + GKISFS
-
-
-
-
?
ISG15-nsp2-fusion protein + H2O
?
MHV substrate
?
-
-
-
-
?
N-benzoyl-Phe-Val-Arg-4-nitroanilide + H2O
N-benzoyl-Phe-Val-Arg + 4-nitroaniline
-
-
-
?
PLP2-MP1 precursor polyprotein + H2O
MP1 + ?
-
-
-
-
?
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-methylcoumarin + H2O
?
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
-
-
?
ubiquitin-aminomethylcoumarin + H2O
?
-
-
-
?
ubiquitinated branched peptides + H2O
?
-
-
-
-
?
ubiquitinated RIG-I + H2O
deubiquitinated RIG-I + ubiquitin
-
-
-
?
ubiquitinated STING + H2O
deubiquitinated STING + ubiquitin
-
-
-
?
VAKQGAGFKRTY + H2O
VAKQGA + GFKRTY
-
-
-
-
?
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-amido-4-methylcoumarin + H2O
Z-LRGG + 7-amino-4-methylcoumarin
-
-
-
?
additional information
?
-
(E-EDANS)RELNGGAPI(K-DABCYL)S + H2O
?
-
-
-
-
?
(E-EDANS)RELNGGAPI(K-DABCYL)S + H2O
?
-
-
-
-
?
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine + H2O
?
-
fluorogenic substrate
-
-
?
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine + H2O
?
-
fluorogenic substrate
-
-
?
BCoV substrate
?
-
-
-
-
?
BCoV substrate
?
-
-
-
-
?
branched polyubiquitin chains + H2O
?
-
-
-
-
?
branched polyubiquitin chains + H2O
?
-
-
-
-
?
diubiquitin + H2O
?
-
-
-
-
?
diubiquitin + H2O
?
-
-
-
-
?
FRLKGGAPIKGV
?
-
12 mer oligopeptide containing Gly818-Ala819, 100% cleavage
-
-
?
FRLKGGAPIKGV
?
-
12 mer oligopeptide containing Gly818-Ala819, 100% cleavage
-
-
?
ISG15-nsp2-fusion protein + H2O
?
-
-
-
-
?
ISG15-nsp2-fusion protein + H2O
?
-
-
-
-
?
ISLKGGKIVSTC
?
-
12 mer oligopeptide containing Gly2740-Lys2741, 29% cleavage
-
-
?
ISLKGGKIVSTC
?
-
12 mer oligopeptide containing Gly2740-Lys2741, 29% cleavage
-
-
?
ubiquitin + H2O
?
-
-
-
?
ubiquitin + H2O
?
-
the enzyme cleaves the LRGG tail of ubiquitin
-
-
?
ubiquitin + H2O
?
the enzyme processes both K-48 and K-63 linked polyubiquitin chains
-
-
?
ubiquitin-7-amido-4-methylcoumarin + H2O
?
-
-
-
-
?
ubiquitin-7-amido-4-methylcoumarin + H2O
?
-
-
-
-
?
Z-LRGG-7-amido-4-methylcoumarin + H2O
?
-
-
-
-
?
Z-LRGG-7-amido-4-methylcoumarin + H2O
?
-
-
-
-
?
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
?
-
-
Cys1715 is a catalytic residue of PLP2
-
-
?
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
-
-
?
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(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
hydroxypridine-2-thione Zn
-
-
hydroxypyridine-2-thione-Zn(II)
-
-
-
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-phenyldithiocarbaic acid Zn
-
-
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
-
6-Mercaptopurine
competitive and reversible inhibitor
6-thioguanine
noncompetitive
6-thioguanine
competitive and reversible inhibitor
Cu2+
-
weakly inhibited by 70% at 0.01 mM
Cu2+
-
30% inhibition at 0.01 mM
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
-
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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
Crystal structure of SCCA1 and insight about the interaction with JNK1.
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
Identification of mouse hepatitis virus papain-like proteinase 2 activity.
Hepatitis
Identification of the murine coronavirus p28 cleavage site.
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.
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0.021 - 0.0772
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine
0.0396 - 0.0616
Dabcyl-FKKKGGGDVKE-Edans
0.0186 - 0.0321
Dabcyl-FRLKGGAPIKGV-Edans
0.09687 - 0.1769
N-benzoyl-Phe-Val-Arg-4-nitroanilide
0.73 - 3.33
ubiquitin-7-amido-4-trifluoromethylcoumarin
-
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
additional information
additional information
-
0.021
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine
-
at pH 5.25
0.064
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine
-
at pH 6.05
0.0654
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine
-
at pH 6.82
0.068
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine
-
at pH 9.2
0.0704
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine
-
at pH 9.8
0.0714
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine
-
at pH 8.65
0.072
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine
-
at pH 8.01
0.0772
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine
-
at pH 7.42
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.
0.023 - 0.366
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine
0.0041 - 0.005
Dabcyl-FKKKGGGDVKE-Edans
0.0011 - 0.0175
Dabcyl-FRLKGGAPIKGV-Edans
0.23 - 2.65
N-benzoyl-Phe-Val-Arg-4-nitroanilide
0.01 - 0.79
ubiquitin-7-amido-4-trifluoromethylcoumarin
-
0.023
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine
-
at pH 5.25
0.1
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine
-
at pH 9.8
0.198
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine
-
at pH 6.05
0.233
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine
-
at pH 9.2
0.33
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine
-
at pH 7.42
0.343
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine
-
at pH 6.82
0.363
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine
-
at pH 8.01
0.366
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine
-
at pH 8.65
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.
0.082 - 0.103
Dabcyl-FKKKGGGDVKE-Edans
0.055 - 0.058
Dabcyl-FRLKGGAPIKGV-Edans
1.8 - 14.87
N-benzoyl-Phe-Val-Arg-4-nitroanilide
0.045 - 0.155
RLRGG-7-amido-4-methylcoumarin
0.01 - 1.08
ubiquitin-7-amido-4-trifluoromethylcoumarin
-
0.413 - 17
ubiquitin-aminomethylcoumarin
-
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
recombinant mutant E168A, pH 7.4, 30°C
-
0.36
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant mutant L163Q, pH 7.4, 30°C
-
0.45
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant mutant Y265F, pH 7.4, 30°C
-
0.55
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant mutant E168D, pH 7.4, 30°C
-
1.01
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant mutant E168R, pH 7.4, 30°C
-
1.08
ubiquitin-7-amido-4-trifluoromethylcoumarin
recombinant wild-type enzyme, pH 7.4, 30°C
-
0.413
ubiquitin-aminomethylcoumarin
mutant enzyme I353R, at pH 8.0 and 37°C
-
1.741
ubiquitin-aminomethylcoumarin
mutant enzyme I353W, at pH 8.0 and 37°C
-
17
ubiquitin-aminomethylcoumarin
wild type enzyme, at pH 8.0 and 37°C
-
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0.0041
(4E)-1,7-bis(3,4-dihydroxyphenyl)hept-4-en-3-one
Severe acute respiratory syndrome-related coronavirus
-
pH and temperature not specified in the publication
0.005
(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
Severe acute respiratory syndrome-related coronavirus
-
pH and temperature not specified in the publication
0.0008
1,6,6-trimethyl-1,2,6,7,8,9-hexahydrophenanthro[1,2-b]furan-10,11-dione
Severe acute respiratory syndrome-related coronavirus
-
pH and temperature not specified in the publication
0.0087
2-methyl-N-[(1R)-1-(naphthalen-2-yl)ethyl]benzamide
Severe acute respiratory syndrome-related coronavirus
-
pH and temperature not specified in the publication
0.0201
2-methyl-N-[1-(naphthalen-2-yl)ethyl]benzamide
Severe acute respiratory syndrome-related coronavirus
-
racemate, pH and temperature not specified in the publication
0.0006
5-amino-2-methyl-N-[(1R)-1-(naphthalen-1-yl)ethyl]benzamide
Severe acute respiratory syndrome-related coronavirus
-
pH and temperature not specified in the publication
0.0216 - 0.0581
6-Mercaptopurine
0.005 - 0.0137
6-thioguanine
0.0001712 - 0.000349
E-64
0.0037
hydroxypyridine-2-thione-Zn(II)
Severe acute respiratory syndrome-related coronavirus
-
pH and temperature not specified in the publication
-
0.00032
N-(1,3-benzodioxol-5-ylmethyl)-1-[(1R)-1-(naphthalen-1-yl)ethyl]piperidine-4-carboxamide
Severe acute respiratory syndrome-related coronavirus
-
pH and temperature not specified in the publication
0.00015
N-(3-fluorobenzyl)-1-[(1R)-1-(naphthalen-1-yl)ethyl]piperidine-4-carboxamide
Severe acute respiratory syndrome-related coronavirus
-
pH and temperature not specified in the publication
0.00049
N-(4-fluorobenzyl)-1-[(1R)-1-(naphthalen-1-yl)ethyl]piperidine-4-carboxamide
Severe acute respiratory syndrome-related coronavirus
-
pH and temperature not specified in the publication
0.059
N-(4-methoxybenzyl)-1-(naphthalen-1-ylmethyl)piperidine-4-carboxamide
Severe acute respiratory syndrome-related coronavirus
-
pH and temperature not specified in the publication
0.0033
N-ethyl-N-phenyldithiocarbamic acid-Zn(II)
Severe acute respiratory syndrome-related coronavirus
-
pH and temperature not specified in the publication
-
0.00035
N-[(2-methoxypyridin-4-yl)methyl]-1-[(1R)-1-(naphthalen-1-yl)ethyl]piperidine-4-carboxamide
Severe acute respiratory syndrome-related coronavirus
-
pH and temperature not specified in the publication
0.00039
N-[3-(acetylamino)benzyl]-1-[(1R)-1-(naphthalen-1-yl)ethyl]piperidine-4-carboxamide
Severe acute respiratory syndrome-related coronavirus
-
pH and temperature not specified in the publication
0.0216
6-Mercaptopurine
Severe acute respiratory syndrome-related coronavirus
-
pH and temperature not specified in the publication
0.0581
6-Mercaptopurine
porcine epidemic diarrhea virus
pH 6.5, 30°C
0.005
6-thioguanine
Severe acute respiratory syndrome-related coronavirus
-
pH and temperature not specified in the publication
0.0137
6-thioguanine
porcine epidemic diarrhea virus
pH 6.5, 30°C
0.0001712
E-64
Tabernaemontana divaricata
mutant enzyme S32T/A67Y, in 50 mM Na-acetate buffer pH 5.0, at 60°C
0.0002137
E-64
Tabernaemontana divaricata
mutant enzyme S32T, in 50 mM Na-acetate buffer pH 5.0, at 60°C
0.0002507
E-64
Tabernaemontana divaricata
mutant enzyme A67Y, in 50 mM Na-acetate buffer pH 5.0, at 60°C
0.000349
E-64
Tabernaemontana divaricata
wild type enzyme, in 50 mM Na-acetate buffer pH 5.0, at 60°C
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malfunction
arteriviruses lacking PLP2 deubiquitinase activity elicit an enhanced host innate immune response
malfunction
mutations of residues in the enzyme-ubiquitin interface lead to reduced catalytic activity
physiological function
-
papain-like protease domain 2 (PLP2) deubiquitinates TANK-binding kinase-1 (TBK1) and reduces its kinase activity, hence inhibits interferon-beta reporter activity and prevents interferon regulatory factor 3 (IRF3) nuclear translocation. The presence of PLP2 stabilizes the hypo-phosphorylated IRF3-TBK1 complex in a dose-dependent manner in the cytoplasm
physiological function
-
PLP2 is responsible for the inhibition of both RIG-I and TLR3-dependent induction of interferon alpha/beta expression
physiological function
the enzyme is essential for arterivirus replication by cleaving a site within the viral replicase polyproteins and also removes ubiquitin from cellular proteins. This deubiquitinase activity is a critical factor in arteriviral innate immune evasion
physiological function
the enzyme is one of two cysteine proteases involved in the proteolytic processing of the polyproteins of Severe acute respiratory syndrome coronavirus. It also shows significant in vitro deubiquitinating and de-ISGylating activities
physiological function
the enzyme strongly inhibits RIG-Iand STING-activated interferon expression. Papain-like protease 2 acts as a viral deubiquitinase to interfere with the RIG-I- and STING-mediated signalling pathway
physiological function
-
the primary function of the enzyme is to process the viral polyprotein in a coordinated manner. An additional function of the enzyme is stripping ubiquitin and ISG15 from host-cell proteins to aid the coronavirus in the evasion of the host innate immune responses, enzyme innate immune functions, overview
physiological function
-
changes within the Ubl domain, residues 785 to 787 of nonstructural protein 3, negatively affect protease activity. Ubl mutant viruses V787S and V785S replicate efficiently at 37°C but generate smaller plaques than wild-type virus, and V787S is defective for replication at higher temperatures. The proteases of the mutant viruses exhibit similar specific activities at 25°C but diplay significantly reduced thermal stability at 30°C, thereby reducing the total enzymatic activity. Infection of C57BL/6 mice with V787S is highly attenuated, yet it replicates sufficiently to elicit protective immunity
additional information
-
enzyme structure and function, active site structure with catalytic triad residues, Cys112, His273 and Asp287 and the oxyanion hole-stabilizing residue Trp107, and catalytic mechanism, detailed overview. The fingers domain of PLpro, which contains a zinc ion that is tetrahedrally coordinated by four cysteines, is essential for catalysis because it maintains the structural integrity of the enzyme
additional information
the enzyme comprises the viral polyprotein residues 1541-1858
additional information
-
the enzyme comprises the viral polyprotein residues 1541-1858
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hanging-drop vapor-diffusion, to 1.85 A resolution, the enzyme has an intact zinc-binding motif, an unobstructed catalytically competent active site and an intriguing, ubiquitin-like N-terminal domain
-
in complex with ubiquitin, hanging drop vapor diffusion method, using 100 mM MES, pH 6.2, 18% (w/v) polyethylene glycol 20,000
hanging drop vapor diffusion method, using 100 mM Bis-Tris, pH 6.5, 25-30% (w/v) polyethylene glycol monomethyl ether 2000
apoenzyme and enzyme in complexes with ubiquitin, and inhibitors 5-amino-2-methyl-N-[(1R)-1-(naphthalen-1-yl)ethyl]benzamide, N-(1,3-benzodioxol-5-ylmethyl)-1-[(1R)-1-(naphthalen-1-yl)ethyl]piperidine-4-carboxamide, N-(4-fluorobenzyl)-1-[(1R)-1-(naphthalen-1-yl)ethyl]piperidine-4-carboxamide, and N-(3-fluorobenzyl)-1-[(1R)-1-(naphthalen-1-yl)ethyl]piperidine-4-carboxamide, sitting drop vapor diffusion method, apoenzyme by mixing of 1.1-20 mg/ml protein in 20 mM Tris, pH 7.5, 10 mM DTT, with 100 mM sodium citrate, pH 5.2, 3 M ammonium sulfate. Enzyme-inhibitor N-(1,3-benzodioxol-5-ylmethyl)-1-[(1R)-1-(naphthalen-1-yl)ethyl]piperidine-4-carboxamide complex by mixing of 5 mg/ml protein in 20 mM Tris, pH 7.5, 10 mM DTT, with 1 mM inhibitor, 1 M (NH4)2SO4, 50 mM MES, pH 6.5, and 2.5% PEG 400. Enzyme-inhibitor 5-amino-2-methyl-N-[(1R)-1-(naphthalen-1-yl)ethyl]benzamide by mixing of 8 mg/ml protein in 20 mM Tris, pH 7.5, 10 mM DTT with 0.20 mM inhibitor, 1 M LiCl2, 0.1 M MES pH 6.0, 30% PEG 6000. Enzyme-inhibitor N-(3-fluorobenzyl)-1-[(1R)-1-(naphthalen-1-yl)ethyl]piperidine-4-carboxamide or N-(4-fluorobenzyl)-1-[(1R)-1-(naphthalen-1-yl)ethyl]piperidine-4-carboxamide complex by mixing of 6 and 12 mg/ml protein, respectively, in 25 mM Tris, pH 7.5, 100 mM NaCl, 10 mM DTT with 0.20 mM inhibitor, 100 mM sodium citrate, pH 5.5, 40% v/v PEG 600. Enzyme-ubiquitin complex by mixing of 3-12 mg/ml protein and ubiquitin in 20 mM Tris, pH 7.5, with 0.1 M CHES, pH 9.5, 18% PEG 3000, X-ray diffraction structure determination and analysis at 1.4-2.75 A resolution
-
purified enzyme mutant C112S in complex with ubiquitin, sitting drop vapour diffusion method, mixing of enzyme and ubiquitin in a 1:1 molar ratio giving 8 mg/ml and 2 mg/ml, respectively, addition of a reservoir solution consisting of 18% PEG 3000, 0.1 M CHES, pH 9.5, 22°C, X-ray diffraction structure determination and analysis at 1.4 A resolution
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C1732A
-
encodes a substitution of a cysteine residue, predicted to be critical for zinc binding
D1826A
-
purified SARS-CoV PLpro protein containing an alanine substitution at putative catalytic residues
C1732A
-
encodes a substitution of a cysteine residue, predicted to be critical for zinc binding
-
D1826A
-
purified SARS-CoV PLpro protein containing an alanine substitution at putative catalytic residues
-
C270A/H332A
active site mutant
I353R
the mutant exhibits about 40fold reduction in specificity toward ubiquitin compared to the wild type while the activity toward RLRGG-7-amido-4-methylcoumarin is essentially unaltered
I353W
the mutant exhibits about 10fold reduction in specificity toward ubiquitin compared to the wild type while the activity toward RLRGG-7-amido-4-methylcoumarin is essentially unaltered
C1729A
the mutant shows reduced interferon antagonistic activity compared to that of the wild type enzyme
D1901A
the mutant almost completely loses interferon antagonistic activity compared to that of the wild type enzyme
H1888A
the mutant almost completely loses interferon antagonistic activity compared to that of the wild type enzyme
T39W
mutation enhances hydrolysis of the SARS-CoV-derived peptidyl substrate Dabcyl-FRLKGGAPIKGV-Edans
D165A
site-directed mutagenesis, the mutant shows reduced activity in deubiquitination compared to the wild-type enzyme
E168A
site-directed mutagenesis, the mutant shows reduced activity in deubiquitination compared to the wild-type enzyme
E168D
site-directed mutagenesis, the mutant shows reduced activity in deubiquitination compared to the wild-type enzyme
E168R
site-directed mutagenesis, the mutant shows reduced activity in deubiquitination compared to the wild-type enzyme
L163Q
site-directed mutagenesis, the mutant shows reduced activity in deubiquitination compared to the wild-type enzyme
Y265A
site-directed mutagenesis, the mutant shows reduced activity in deubiquitination compared to the wild-type enzyme
Y265F
site-directed mutagenesis, the mutant shows reduced activity in deubiquitination compared to the wild-type enzyme
Y274A
site-directed mutagenesis, inactive mutant
A67Y
the mutation enhances the catalytic efficiency of the enzyme about 8fold while the thermostability of the mutant enzyme remains unchanged. The specific activity against azo-casein is almost 2.4 times higher than wild type
S32T
the mutation enhances the catalytic efficiency of the enzyme about 8fold while the thermostability of the mutant enzyme remains unchanged
S32T/A67Y
the mutations enhance the catalytic efficiency of the enzyme about 8fold while the thermostability of the mutant enzyme remains unchanged
C1651A
-
Plpro active-site mutant
C1651A
-
purified SARS-CoV PLpro protein containing an alanine substitution at putative catalytic residues
C1651A
-
purified SARS-CoV PLpro protein containing an alanine substitution at putative catalytic residues
-
C1651A
-
Plpro active-site mutant
-
T312A/I313V/I353R
the mutant shows the greatest decrease in inhibitory activity in the interferon-beta promoter activity assay
T312A/I313V/I353R
mutant lacks deubiquitinase activity, amino acid numbering based on polyprotein
T312A/I313V/I353R
-
mutant lacks deubiquitinase activity, amino acid numbering based on polyprotein
-
C112S
-
site-directed mutagenesis, active site cysteine mutant, forms a noncovalent complex with ubiquitin, crystal structure analysis
C112S
site-directed mutagenesis, the C112S mutant is monomeric, ubiquitin binding crystal structure analysis, overview
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Expression of murine coronavirus recombinant papain-like proteinase: efficient cleavage is dependent on the lengths of both the substrate and the proteinase polypeptide
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Murine coronavirus
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Alphacoronavirus, Alphacoronavirus SARS-CoV
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Coronavirus papain-like endopeptidases
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2
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2004
Alphacoronavirus
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The papain-like protease of severe acute respiratory syndrome coronavirus has deubiquitinating activity
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2005
Alphacoronavirus, Alphacoronavirus SARS-CoV
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The papain-like protease from the severe acute respiratory syndrome coronavirus is a deubiquitinating enzyme
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2005
Alphacoronavirus, Alphacoronavirus SARS-CoV
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Severe acute respiratory syndrome coronavirus papain-like protease: structure of a viral deubiquitinating enzyme
Proc. Natl. Acad. Sci. USA
103
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2006
Alphacoronavirus, Alphacoronavirus SARS-CoV
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Human coronavirus 229E
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2011
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PLP2 of mouse hepatitis virus A59 (MHV-A59) targets TBK1 to negatively regulate cellular type I interferon signaling pathway
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6
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Murine hepatitis virus
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Deubiquitinase activity and regulation of antiviral innate immune responses by papain-like proteases of human coronavirus NL63
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37
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2010
Human coronavirus NL63
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Structural basis for catalysis and ubiquitin recognition by the severe acute respiratory syndrome coronavirus papain-like protease
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70
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2014
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The SARS-coronavirus papain-like protease: structure, function and inhibition by designed antiviral compounds
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Severe acute respiratory syndrome-related coronavirus
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8
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Tabernaemontana divaricata (P83654), Tabernaemontana divaricata
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Deubiquitinase function of arterivirus papain-like protease 2 suppresses the innate immune response in infected host cells
Proc. Natl. Acad. Sci. USA
110
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Porcine epidemic diarrhea virus papain-like protease 2 can be noncompetitively inhibited by 6-thioguanine
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158
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