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Information on EC 3.4.22.B50 - papain-like proteinase 2
for references in articles please use BRENDA:EC3.4.22.B50
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preliminary BRENDA-supplied EC number
EC Tree 3 Hydrolases
3.4 Acting on peptide bonds (peptidases)
3.4.22 Cysteine endopeptidases
3.4.22.B50 papain-like proteinase 2
The enzyme appears in viruses and cellular organisms
- 3.4.22.B50
- polyproteins
-
replicase
- coronaviruses
- 3clpro
- isg15
-
3c-like
-
mhv-a59
- nsp3
- coronaviral
- pp1ab
- medicine
- drug development
Reaction Schemes
showresponsible 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, papain-like protease domain 2, erv-c, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
mouse hepatitis virus papain-like proteinase 2
-
-
-
-
papain-like protease
papain-like protease 2
papain-like protease domain 2
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a catalytic domain of the nonstructural protein 3 of mouse hepatitis virus A59
papain-like proteinase
PL2-PRO
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-
-
-
PLP-2
-
-
-
-
PLP2
PLpro
SARS-coronavirus papain-like protease
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-
severe acute respiratory syndrome coronavirus papain-like protease
-
papain-like protease 2
porcine reproductive and respiratory syndrome virus isolate Pig/United States/SD 01-08/2001
-
-
PLP2
-
-
-
-
PLP2
-
papain-like protease core domain 2 is part of non-structural protein 3
PLP2
porcine reproductive and respiratory syndrome virus isolate Pig/United States/SD 01-08/2001
-
-
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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
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
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-
-
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CAS REGISTRY NUMBER
COMMENTARY
851883-30-2
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
coronavirus viral polyprotein + H2O
?
Substrates: -
Products: -
Products: -
?
Dabcyl-FKKKGGGDVKE-Edans + H2O
?
Substrates: -
Products: -
Products: -
?
Dabcyl-FRLKGGAPIKGV-Edans + H2O
?
Substrates: SARS-CoV-derived substrate
Products: -
Products: -
?
di-ubiquitin + H2O
2 ubiquitin
Substrates: analysis of DUB activity of PEDV PLP2 with a panel of seven lysine-linked di-Ubs (at Lys6, Lys11, Lys27, Lys29, Lys33, Lys48 and Lys63) and linear di-Ub. PEDV PLP2 has significant activity towards Lys63-, Lys48-, Lys11-, and Lys63-linked di-Ub
Products: -
Products: -
?
FRLKGG-4-nitroanilide + H2O
FRLKGG + 4-nitroaniline
Substrates: -
Products: -
Products: -
?
human ISG15-7-amido-4-methylcoumarin + H2O
human ISG15 + 7-amino-4-methylcoumarin
Substrates: -
Products: -
Products: -
?
ISG15-7-amido-4-methylcoumarin + H2O
ISG15 + 7-amino-4-methylcoumarin
-
Substrates: -
Products: -
Products: -
?
N-benzoyl-Phe-Val-Arg-4-nitroanilide + H2O
N-benzoyl-Phe-Val-Arg + 4-nitroaniline
Substrates: -
Products: -
Products: -
?
nsp1-eGFP + H2O
nsp1 + eGFP
-
Substrates: recombinant fusion substrate, Enzyme SADSCoV PLP2 recognizes and processes the cleavage site KRGG of nsp1/nsp2
Products: -
Products: -
?
replicase polyprotein + H2O
?
-
Substrates: 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
Products: -
Products: -
?
RLRGG + H2O
?
Substrates: short peptide sequence
Products: -
Products: -
?
RLRGG-7-amido-4-methylcoumarin + H2O
RLRGG + 7-amino-4-methylcoumarin
Substrates: -
Products: -
Products: -
?
ubiquitin-7-amido-4-trifluoro-methyl-coumarin + H2O
ubiquitin + 7-amino-4-trifluoro-methyl-coumarin
Substrates: -
Products: -
Products: -
?
ubiquitin-7-amido-4-trifluoromethylcoumarin + H2O
ubiquitin + 7-amino-4-trifluoromethylcoumarin
Substrates: 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
Products: -
Products: -
?
ubiquitin-aminomethylcoumarin + H2O
?
Substrates: -
Products: -
Products: -
?
ubiquitinated RIG-I + H2O
deubiquitinated RIG-I + ubiquitin
Substrates: -
Products: -
Products: -
?
ubiquitinated STING + H2O
deubiquitinated STING + ubiquitin
Substrates: -
Products: -
Products: -
?
viral replicase polyprotein + H2O
?
-
Substrates: 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.
Products: -
Products: -
?
Z-KAGG-7-amido-4-methylcoumarin + H2O
Z-KAGG + 7-amino-4-methylcoumarin
-
Substrates: -
Products: -
Products: -
?
(E-EDANS)RELNGGAPI(K-DABCYL)S + H2O
?
-
Substrates: -
Products: -
Products: -
?
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine + H2O
?
-
Substrates: fluorogenic substrate
Products: -
Products: -
?
Abz-FRLKGGAPIKGV-N-(2,4-dinitrophenyl)-ethylenediamine + H2O
?
-
Substrates: fluorogenic substrate
Products: -
Products: -
?
branched polyubiquitin chains + H2O
?
-
Substrates: -
Products: -
Products: -
?
FRLKGGAPIKGV
?
-
Substrates: 12 mer oligopeptide containing Gly818-Ala819, 100% cleavage
Products: -
Products: -
?
FRLKGGAPIKGV
?
-
Substrates: 12 mer oligopeptide containing Gly818-Ala819, 100% cleavage
Products: -
Products: -
?
ISLKGGKIVSTC
?
-
Substrates: 12 mer oligopeptide containing Gly2740-Lys2741, 29% cleavage
Products: -
Products: -
?
ISLKGGKIVSTC
?
-
Substrates: 12 mer oligopeptide containing Gly2740-Lys2741, 29% cleavage
Products: -
Products: -
?
polyubiquitin + H2O
monoubiquitin + ?
Substrates: the enzyme cleaves Lys48- and Lys63-linked polyubiquitin to monoubiquitin but not linear polyubiquitin
Products: -
Products: -
?
polyubiquitin + H2O
monoubiquitin + ?
-
Substrates: the enzyme cleaves Lys48- and Lys63-linked polyubiquitin to monoubiquitin but not linear polyubiquitin
Products: -
Products: -
?
RELNGGAVTRYV + H2O
AVTYRV + RELNGG
-
Substrates: 12 mer oligopeptide containing Gly180-Ala181, 5% cleavage
Products: -
Products: -
?
RELNGGAVTRYV + H2O
AVTYRV + RELNGG
-
Substrates: 12 mer oligopeptide containing Gly180-Ala181, 5% cleavage
Products: -
Products: -
?
ubiquitin + H2O
?
-
Substrates: the enzyme cleaves the LRGG tail of ubiquitin
Products: -
Products: -
?
ubiquitin + H2O
?
Substrates: the enzyme processes both K-48 and K-63 linked polyubiquitin chains
Products: -
Products: -
?
ubiquitin-7-amido-4-methylcoumarin + H2O
?
-
Substrates: -
Products: -
Products: -
?
ubiquitin-7-amido-4-methylcoumarin + H2O
?
-
Substrates: -
Products: -
Products: -
?
ubiquitin-7-amido-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
Substrates: -
Products: -
Products: -
?
ubiquitin-7-amido-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
Substrates: -
Products: -
Products: -
?
ubiquitin-7-amido-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
porcine reproductive and respiratory syndrome virus isolate Pig/United States/SD 01-08/2001
Substrates: -
Products: -
Products: -
?
ubiquitin-7-amido-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
-
Substrates: -
Products: -
Products: -
?
Z-KKAG-7-amido-4-methylcoumarin + H2O
Z-KKAG + 7-amino-4-methylcoumarin
Substrates: the catalytic efficiency toward Z-KKAG-7-amido-4-methylcoumarin is 5times higher than that for Z-LRGG-7-amido-4-methylcoumarin
Products: -
Products: -
?
Z-KKAG-7-amido-4-methylcoumarin + H2O
Z-KKAG + 7-amino-4-methylcoumarin
-
Substrates: the catalytic efficiency toward Z-KKAG-7-amido-4-methylcoumarin is 5times higher than that for Z-LRGG-7-amido-4-methylcoumarin
Products: -
Products: -
?
Z-LRGG-7-amido-4-methylcoumarin + H2O
?
-
Substrates: -
Products: -
Products: -
?
Z-LRGG-7-amido-4-methylcoumarin + H2O
Z-LRGG + 7-amino-4-methylcoumarin
Substrates: -
Products: -
Products: -
?
Z-LRGG-7-amido-4-methylcoumarin + H2O
Z-LRGG + 7-amino-4-methylcoumarin
-
Substrates: -
Products: -
Products: -
?
Z-LRGG-7-amido-4-methylcoumarin + H2O
Z-LRGG + 7-amino-4-methylcoumarin
-
Substrates: -
Products: -
Products: -
?
additional information
?
-
-
Substrates: SARS-CoV PLP2 does not cleave HCoV.229E and IBV substrates
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: the core domain of PLP2 has in vivo deubiquitinase and DeISGylation activity
Products: -
Products: -
?
additional information
?
-
Substrates: the enzyme cannot cleave Z-KAGG-7-amido-4-methylcoumarin
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme cannot cleave Z-KAGG-7-amido-4-methylcoumarin
Products: -
Products: -
?
additional information
?
-
-
Substrates: Cys1715 is a catalytic residue of PLP2
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme is one of three distinct viral proteases (PLP1, PLP2 and 3CLpro) involved in processing of the replicase polyprotein
Products: -
Products: -
?
additional information
?
-
Substrates: PEDV PLP2 is a deubiquitinase and readily processes a variety of di-Ub linkages. The Betacoronavirus counterparts in comparison have a narrower range of di-Ub activity but process both Ub and ISG15
Products: -
Products: -
-
additional information
?
-
Substrates: PEDV PLP2 displays efficient activity on K6- and K11-linked di-Ub substrates and moderate activity on K48- and K63-linked di-Ub substrates, whereas there are no detectable activities on M1-, K27-, K29-, and K33-linked di-Ub substrates during the course of the experiment. The Ub chain preference for PEDV PLP2 may govern the recognition of the specific polyubiquitinated proteins in host cells
Products: -
Products: -
-
additional information
?
-
Substrates: single-point kinetic parameters are assessed utilizing a 7-amino-4-methylcoumarin (AMC) fluorophore conjugated to the C-terminal end of Ub, human ISG15 and a short peptide sequence, RLRGG. Deubiquitinating and deISGylating substrate preferences are determined by monitoring the release of the AMC fluorophore over time, overview. The suicide substrate Ub-PA binds covalently to PLPs
Products: -
Products: -
-
additional information
?
-
Substrates: analytical ultracentrifugation (AUC) analyses confirmed a complex formed by the PEDV PLP2 C44S mutant and the Ub monomer. The C-terminal tail of Ub inserts into a narrow groove between the palm and thumb domains of PEDV PLP2, also direct interaction of the Ub core region with the thumb and finger domains of PEDV PLP2 occurs, the BL2 region, between beta8 and beta9 of the palm domain, regulates substrate selectivity and binding affinity, detailed overview
Products: -
Products: -
-
additional information
?
-
-
Substrates: enzyme SADS-CoV PLP2 cleaves nsp1 proteins and also peptides mimicking the nsp2/nsp3 cleavage site and also has deubiquitinating and deISGynating activity in in vitro assays. SADS-CoV PLP2 can cleave at the nsp1/nsp site and nsp2/nsp3 site, whose P1-P4 positions are occupied by the KRGG peptide
Products: -
Products: -
-
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
coronavirus viral polyprotein + H2O
?
Substrates: -
Products: -
Products: -
?
replicase polyprotein + H2O
?
-
Substrates: 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
Products: -
Products: -
?
ubiquitinated RIG-I + H2O
deubiquitinated RIG-I + ubiquitin
Substrates: -
Products: -
Products: -
?
ubiquitinated STING + H2O
deubiquitinated STING + ubiquitin
Substrates: -
Products: -
Products: -
?
polyubiquitin + H2O
monoubiquitin + ?
Substrates: the enzyme cleaves Lys48- and Lys63-linked polyubiquitin to monoubiquitin but not linear polyubiquitin
Products: -
Products: -
?
polyubiquitin + H2O
monoubiquitin + ?
-
Substrates: the enzyme cleaves Lys48- and Lys63-linked polyubiquitin to monoubiquitin but not linear polyubiquitin
Products: -
Products: -
?
ubiquitin + H2O
?
-
Substrates: the enzyme cleaves the LRGG tail of ubiquitin
Products: -
Products: -
?
ubiquitin + H2O
?
Substrates: the enzyme processes both K-48 and K-63 linked polyubiquitin chains
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme is one of three distinct viral proteases (PLP1, PLP2 and 3CLpro) involved in processing of the replicase polyprotein
Products: -
Products: -
?
additional information
?
-
Substrates: PEDV PLP2 is a deubiquitinase and readily processes a variety of di-Ub linkages. The Betacoronavirus counterparts in comparison have a narrower range of di-Ub activity but process both Ub and ISG15
Products: -
Products: -
-
additional information
?
-
Substrates: PEDV PLP2 displays efficient activity on K6- and K11-linked di-Ub substrates and moderate activity on K48- and K63-linked di-Ub substrates, whereas there are no detectable activities on M1-, K27-, K29-, and K33-linked di-Ub substrates during the course of the experiment. The Ub chain preference for PEDV PLP2 may govern the recognition of the specific polyubiquitinated proteins in host cells
Products: -
Products: -
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
additional information
-
no effect by Mg2+, Ca2+, Mn2+, Co2+, and Ni2+
Zn2+
eight of the zinc ions are associated with the finger domain of PEDV PLP2, whereas six zinc ions form electrostatic bridges between the chains of PEDV PLP2. Four of the zinc ions form bridges between the cloning remnant His-3 and His1692 of chains A, C, G and E and Cys1812 of chains O, M, I and K. The other two zinc ions form bridges between Glu1803 and Cys1812 in chains C and E and Glu1803 and Cys1812 in chains A and G
Zn2+
-
the fingers domain of the enzyme contains a zinc ion that is tetrahedrally coordinated by four cysteines
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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
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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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.
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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
0.0396
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
0.0006199
ISG15-7-amido-4-methylcoumarin
-
recombinant wild-type enzyme, pH 7.5, 24°C
-
0.0006308
ISG15-7-amido-4-methylcoumarin
-
recombinant mutant H256A, pH 7.5, 24°C
-
0.0006467
ISG15-7-amido-4-methylcoumarin
-
recombinant mutant DELTAN49, pH 7.5, 24°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
0.0003206
ubiquitin-7-amido-4-methylcoumarin
-
recombinant mutant DELTAN49, pH 7.5, 24°C
-
0.0003416
ubiquitin-7-amido-4-methylcoumarin
-
recombinant wild-type enzyme, pH 7.5, 24°C
-
0.0003692
ubiquitin-7-amido-4-methylcoumarin
-
recombinant mutant D269A, pH 7.5, 24°C
-
0.0004532
ubiquitin-7-amido-4-methylcoumarin
-
recombinant mutant F83A, pH 7.5, 24°C
-
0.0004732
ubiquitin-7-amido-4-methylcoumarin
-
recombinant mutant H256A, pH 7.5, 24°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
-
0.00879
Z-KAGG-7-amido-4-methylcoumarin
-
recombinant wild-type enzyme, pH 7.5, 24°C
-
0.01757
Z-KAGG-7-amido-4-methylcoumarin
-
recombinant mutant DELTAN49, pH 7.5, 24°C
-
0.028
Z-KAGG-7-amido-4-methylcoumarin
-
recombinant mutant N99A, pH 7.5, 24°C
-
0.032
Z-KAGG-7-amido-4-methylcoumarin
-
recombinant mutant Y257A, pH 7.5, 24°C
-
0.0356
Z-KAGG-7-amido-4-methylcoumarin
-
recombinant mutant D98A, pH 7.5, 24°C
-
0.0167
Z-LRGG-7-amido-4-methylcoumarin
-
recombinant mutant Y257A, pH 7.5, 24°C
0.0178
Z-LRGG-7-amido-4-methylcoumarin
-
recombinant mutant F83A, pH 7.5, 24°C
0.0191
Z-LRGG-7-amido-4-methylcoumarin
-
recombinant mutant D98A, pH 7.5, 24°C
0.0282
Z-LRGG-7-amido-4-methylcoumarin
-
recombinant mutant W102A, pH 7.5, 24°C
0.03734
Z-LRGG-7-amido-4-methylcoumarin
-
recombinant wild-type enzyme, pH 7.5, 24°C
0.042
Z-LRGG-7-amido-4-methylcoumarin
-
recombinant mutant DELTAN49, pH 7.5, 24°C
0.0442
Z-LRGG-7-amido-4-methylcoumarin
-
recombinant mutant D269A, pH 7.5, 24°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
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
-
additional information
additional information
Michaelis-Menten kinetics of deubiquitinase activity
-
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
0.042
ISG15-7-amido-4-methylcoumarin
-
recombinant mutant H256A, pH 7.5, 24°C
-
0.0656
ISG15-7-amido-4-methylcoumarin
-
recombinant wild-type enzyme, pH 7.5, 24°C
-
0.0895
ISG15-7-amido-4-methylcoumarin
-
recombinant mutant DELTAN49, pH 7.5, 24°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
0.00899
ubiquitin-7-amido-4-methylcoumarin
-
recombinant mutant D269A, pH 7.5, 24°C
-
0.00993
ubiquitin-7-amido-4-methylcoumarin
-
recombinant mutant H256A, pH 7.5, 24°C
-
0.0214
ubiquitin-7-amido-4-methylcoumarin
-
recombinant wild-type enzyme, pH 7.5, 24°C
-
0.02508
ubiquitin-7-amido-4-methylcoumarin
-
recombinant mutant DELTAN49, pH 7.5, 24°C
-
0.0354
ubiquitin-7-amido-4-methylcoumarin
-
recombinant mutant F83A, pH 7.5, 24°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
-
0.0073
Z-KAGG-7-amido-4-methylcoumarin
-
recombinant mutant N99A, pH 7.5, 24°C
-
0.0086
Z-KAGG-7-amido-4-methylcoumarin
-
recombinant mutant Y257A, pH 7.5, 24°C
-
0.0118
Z-KAGG-7-amido-4-methylcoumarin
-
recombinant mutant D98A, pH 7.5, 24°C
-
0.0153
Z-KAGG-7-amido-4-methylcoumarin
-
recombinant wild-type enzyme, pH 7.5, 24°C
-
0.0363
Z-KAGG-7-amido-4-methylcoumarin
-
recombinant mutant DELTAN49, pH 7.5, 24°C
-
0.00154
Z-LRGG-7-amido-4-methylcoumarin
-
recombinant mutant D98A, pH 7.5, 24°C
0.0031
Z-LRGG-7-amido-4-methylcoumarin
-
recombinant mutant W102A, pH 7.5, 24°C
0.00389
Z-LRGG-7-amido-4-methylcoumarin
-
recombinant mutant Y257A, pH 7.5, 24°C
0.0085
Z-LRGG-7-amido-4-methylcoumarin
-
recombinant mutant F83A, pH 7.5, 24°C
0.01145
Z-LRGG-7-amido-4-methylcoumarin
-
recombinant wild-type enzyme, pH 7.5, 24°C
0.0122
Z-LRGG-7-amido-4-methylcoumarin
-
recombinant mutant D269A, pH 7.5, 24°C
0.017
Z-LRGG-7-amido-4-methylcoumarin
-
recombinant mutant DELTAN49, pH 7.5, 24°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
66.58
ISG15-7-amido-4-methylcoumarin
-
recombinant mutant H256A, pH 7.5, 24°C, calculated by BRENDA
-
105.82
ISG15-7-amido-4-methylcoumarin
-
recombinant wild-type enzyme, pH 7.5, 24°C, calculated by BRENDA
-
138.4
ISG15-7-amido-4-methylcoumarin
-
recombinant mutant DELTAN49, pH 7.5, 24°C, calculated by BRENDA
-
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
24.35
ubiquitin-7-amido-4-methylcoumarin
-
recombinant mutant D269A, pH 7.5, 24°C, calculated by BRENDA
-
30.98
ubiquitin-7-amido-4-methylcoumarin
-
recombinant mutant H256A, pH 7.5, 24°C, calculated by BRENDA
-
55.65
ubiquitin-7-amido-4-methylcoumarin
-
recombinant mutant F83A, pH 7.5, 24°C, calculated by BRENDA
-
62.65
ubiquitin-7-amido-4-methylcoumarin
-
recombinant wild-type enzyme, pH 7.5, 24°C, calculated by BRENDA
-
78.22
ubiquitin-7-amido-4-methylcoumarin
-
recombinant mutant DELTAN49, pH 7.5, 24°C, calculated by BRENDA
-
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
-
0.0261
Z-KAGG-7-amido-4-methylcoumarin
-
recombinant mutant N99A, pH 7.5, 24°C, calculated by BRENDA
-
0.269
Z-KAGG-7-amido-4-methylcoumarin
-
recombinant mutant Y257A, pH 7.5, 24°C, calculated by BRENDA
-
0.332
Z-KAGG-7-amido-4-methylcoumarin
-
recombinant mutant D98A, pH 7.5, 24°C, calculated by BRENDA
-
1.74
Z-KAGG-7-amido-4-methylcoumarin
-
recombinant wild-type enzyme, pH 7.5, 24°C, calculated by BRENDA
-
2.066
Z-KAGG-7-amido-4-methylcoumarin
-
recombinant mutant DELTAN49, pH 7.5, 24°C, calculated by BRENDA
-
0.0806
Z-LRGG-7-amido-4-methylcoumarin
-
recombinant mutant D98A, pH 7.5, 24°C, calculated by BRENDA
0.11
Z-LRGG-7-amido-4-methylcoumarin
-
recombinant mutant W102A, pH 7.5, 24°C, calculated by BRENDA
0.233
Z-LRGG-7-amido-4-methylcoumarin
-
recombinant mutant Y257A, pH 7.5, 24°C, calculated by BRENDA
0.276
Z-LRGG-7-amido-4-methylcoumarin
-
recombinant mutant D269A, pH 7.5, 24°C, calculated by BRENDA
0.307
Z-LRGG-7-amido-4-methylcoumarin
-
recombinant wild-type enzyme, pH 7.5, 24°C, calculated by BRENDA
0.405
Z-LRGG-7-amido-4-methylcoumarin
-
recombinant mutant DELTAN49, pH 7.5, 24°C, calculated by BRENDA
0.478
Z-LRGG-7-amido-4-methylcoumarin
-
recombinant mutant F83A, pH 7.5, 24°C, calculated by BRENDA
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00049
5-amino-2-methyl-N-[(1R)-1-(naphthalen-1-yl)ethyl]benzamide
-
pH and temperature not specified in the publication
0.015
6-Mercaptopurine
pH 7.4, 30°C
0.015
6-thioguanine
pH 7.4, 30°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
0.0037
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
0.005
6-thioguanine
Severe acute respiratory syndrome-related coronavirus
-
pH and temperature not specified in the publication
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30.78
wild type enzyme, with azocasein as substrate, in 50 mM Na-acetate buffer pH 5.0, at 60°C
63.11
mutant enzyme S32T/A67Y, with azocasein as substrate, in 50 mM Na-acetate buffer pH 5.0, at 60°C
73.63
mutant enzyme S32T, with azocasein as substrate, in 50 mM Na-acetate buffer pH 5.0, at 60°C
86.95
mutant enzyme A67Y, with azocasein as substrate, in 50 mM Na-acetate buffer pH 5.0, at 60°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
replicase polyprotein 1ab; PRRSV
SwissProt
brenda
porcine reproductive and respiratory syndrome virus isolate Pig/United States/SD 01-08/2001
replicase polyprotein 1ab; PRRSV
SwissProt
brenda
from the Guangdong Province of China
-
-
brenda
polyprotein; SARS-CoV
UniProt
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
structural similarity of SADS-CoV PLP2 to SARS-CoV or MERS-CoV PLPro and TGEV PLP1, enzyme sequences and structures comparisons, overview
malfunction
metabolism
physiological function
additional information
malfunction
mutations of residues in the enzyme-ubiquitin interface lead to reduced catalytic activity
malfunction
arteriviruses lacking PLP2 deubiquitinase activity elicit an enhanced host innate immune response
malfunction
mutations of Ub-interacting residues result in a moderately or completely abolished deubiquitinylating function of PEDV PLP2. PEDV PLP2 exhibits a broad substrate preference, superior deubiquitination (DUB) function, and inferior peptidase activity
malfunction
recombinant PRRSV carrying PLP2 DUB-specific mutations faces significant selective pressure to revert to wild-type virus in MARC-145 cells, suggesting that the PLP2 DUB activity, which in PRRSV is present as three different versions of viral protein nsp2 expressed during infection, is critically important for PRRSV replication. Specific PLP2 residues that are critically involved in substrate recognition are under selective pressure to revert to wild-type during infection
malfunction
porcine reproductive and respiratory syndrome virus isolate Pig/United States/SD 01-08/2001
-
recombinant PRRSV carrying PLP2 DUB-specific mutations faces significant selective pressure to revert to wild-type virus in MARC-145 cells, suggesting that the PLP2 DUB activity, which in PRRSV is present as three different versions of viral protein nsp2 expressed during infection, is critically important for PRRSV replication. Specific PLP2 residues that are critically involved in substrate recognition are under selective pressure to revert to wild-type during infection
-
metabolism
the 30-kb single-stranded RNA genome of coronavirus (CoV) encodes two overlapping polyproteins, pp1a and pp1b, that require proteolytic processing to release functional polypeptides. The main protease (Mpro or 3C-like protease) and papain-like protease (PLpro) are the coronaviral enzymes that catalyze the cleavage of viral polyproteins. PLpro is one of the functional domains within nonstructural protein 3 (nsp3) and an essential protease that is expressed in the early stage of CoV infection and mainly mediates the proteolytic release of the first three nsps from the viral polyprotein. These functions of PLpro have been implicated in the virulence traits of coronaviruses, overview
metabolism
deubiquitination of cellular substrates by viral proteases is a mechanism used to interfere with host cellular signaling processes, shared between members of the coronavirus and arterivirus families. In the case of Arteriviruses, deubiquitinating and polyprotein processing activities are accomplished by the virus-encoded papain-like protease 2 (PLP2)
metabolism
porcine reproductive and respiratory syndrome virus isolate Pig/United States/SD 01-08/2001
-
deubiquitination of cellular substrates by viral proteases is a mechanism used to interfere with host cellular signaling processes, shared between members of the coronavirus and arterivirus families. In the case of Arteriviruses, deubiquitinating and polyprotein processing activities are accomplished by the virus-encoded papain-like protease 2 (PLP2)
-
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 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
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 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
-
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
physiological function
the alphacoronavirus porcine epidemic diarrhea virus (PEDV) encodes a multifunctional papain-like protease 2 (PLP2) that has the ability to process the coronavirus viral polyprotein to aid in RNA replication and antagonize the host innate immune response through cleavage of the regulatory proteins ubiquitin (Ub) and/or interferon-stimulated gene product 15 (ISG15) (deubiquitination and deISGylation, respectively). PEDV PLP2 in cells is directly involved in the antagonism of the IFN response and can cleave poly-Ub chains from RIG-I and stimulator of interferon genes (STING)
physiological function
coronaviral papain-like proteases (PLpros) are essential enzymes that mediate not only the proteolytic processes of viral polyproteins during virus replication but also the deubiquitination and deISGylation of cellular proteins that attenuate host innate immune responses. Critical role of PLP2 in CoV maturation
physiological function
specific importance of porcine reproductive and respiratory syndrome virus papain-like protease 2 (PRRSV PLP2) deubiquitinating activity in viral replication. Role of role of PRRSV PLP2 deubiquitinating activity in host immune evasion and of deubiquitinating activity (DUB) of the porcine reproductive and respiratory syndrome virus (PRRSV) PLP2 in the downregulation of cellular interferon production, overview
physiological function
-
coronaviral proteases, including main proteases and papain-like proteases (PLP), have essential roles in polyprotein processing and thus viral maturation. The viral papain-like protease (PLP) domain is contained in nsp3 of coronaviruses and participates in the proteolytic processing of the N-terminal region of the polyproteins. It could cleave nsp1/nsp2, nsp2/nsp3, and nsp3/nsp4 sites, while all sites downstream nsp4 are processed by nsp5. Besides cleaving the polyproteins, PLPs also possess a related enzymatic activity to promote virus replication: deubiquitinating (DUB) and de-ISGylating activities. Enzyme SADS-CoV PLP2 cleaves nsp1 proteins (and peptides mimicking the nsp2/nsp3 cleavage site) and has deubiquitinating and deISGynating activity. Both ubiquitin and ISG15 are involved in preventing viral infection
physiological function
porcine reproductive and respiratory syndrome virus isolate Pig/United States/SD 01-08/2001
-
specific importance of porcine reproductive and respiratory syndrome virus papain-like protease 2 (PRRSV PLP2) deubiquitinating activity in viral replication. Role of role of PRRSV PLP2 deubiquitinating activity in host immune evasion and of deubiquitinating activity (DUB) of the porcine reproductive and respiratory syndrome virus (PRRSV) PLP2 in the downregulation of cellular interferon production, overview
-
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
additional information
PEDV PLP2 has a similar DUB activity to SARS-CoV-2 PLpro, while its deISGylase function resembles that of the vOTU domain of porcine reproductive and respiratory syndrome virus modified live vaccine. Comparison of structure-activity relationships of SADS-CoVand PEDV PLP2s, overview. In the finger domain of PEDV PLP2, two interactions stand out in the interface with Ub. The first is the terminal N atom of Arg1815 of PEDV PLP2 located in beta-strand 9, which interacts with Ala46 of Ub, and the second is an electrostatic interaction between Asp1833 of PEDV PLP2 in beta-strand 11 and His68 of Ub-PA
additional information
crystal structure analysis of papain-like protease 2 (PLP2) of porcine epidemic diarrhea virus (PEDV) in complex with ubiquitin (Ub) reveals that PEDV PLP2 interacts with the Ub substrate mainly through the Ub core region and C-terminal tail. The 2-residue-extended blocking loop 2 at the S4 subsite contributes to the substrate selectivity and binding affinity of PEDV PLP2. The PEDV PLP2 Glu99 residue, conserved in alphacoronavirus PLpros, governs the preference of a positively charged P4 residue of peptidyl substrates. Three Ub core-interacting residues are essential for DUB function, a 2-residue-elongated blocking loop 2 regulates substrate selectivity, and a conserved glutamate residue governs the substrate specificity of PEDV PLP2. Substrate binding and selectivity of PEDV PLP2, structure-function analysis, overview. All three Ub core-interacting residues are important for the DUB function of PEDV PLP2. CoV PLP2 enzymes structure comparisons
additional information
-
hypothetical modelling of the interaction of ubiquitin with the SADS-CoV PLP2 active site based on the structure of SARS-CoV PLpro bound with ubiquitin. SADS-CoV PLP2 includes the spatial proximity Cys101, H256, and Asp269, which are implicated in the catalysis, referred to as the catalytic triad. Cys101 is positioned at the N-terminus of the alpha3 of the thumb domain, while both His256 and Asp269 residues are located in the palm domain. Enzyme active site structure, overview
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). RPOA_PRRSS
Porcine reproductive and respiratory syndrome virus (isolate Pig/United States/SD 01-08/2001)
3838
12
418948
Swiss-Prot
-
R1A_SARS
4382
14
486373
Swiss-Prot
-
R1AB_IBVB
6629
18
744540
Swiss-Prot
Mitochondrion (Reliability: 5)
R1AB_PEDV7
6781
18
753158
Swiss-Prot
-
RPOA_EAVBU
3175
10
345384
Swiss-Prot
-
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
38000
-
SDS-PAGE and Western blot detection with His6-specific antibodies, P-Plpro(C1)-His6 fragment
41000
-
SDS-PAGE and Western blot detection with His6-specific antibodies, P-Plpro(C2)-His6 fragment
60000
-
SDS-PAGE and Western blot detection with His6-specific antibodies, T7-ISG15P-Plpro(C2)-His6 fragment
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
additional information
additional information
the catalytic core of PEDV PLP2 short reveals a mixture of seven alpha-helices, three 3_10-turns and 17 beta-strands, enzyme crystal structure analysis, overview
additional information
the overall architecture of PEDV PLP2 reveals a right-handed structure with a protein moiety of three domains, including the N-terminal thumb, the internal zinc-binding fingers, and the C-terminal palm domains, detailed overview
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
purified PEDV PLP2 bound to ubiquitin, hanging drop vapour diffusion method, mixing of 0.002 ml of 9.0 mg/ml protein in 150 mM NaCl, 25 mM HEPES pH 7.4, 2 mM DTT, and 0.1 mM ZnCl2, with 0.002 ml of reservoir solution containing 0.30 M MgCl2, 0.1 M Tris, and 16% PEG 4000, method optimization, X-ray diffraction structure determination and analysis at 3.1 A resolution
purified PEDV PLP2 mutant C44S in complex with Ub, X-ray diffraction structure determination and analysis
purified apo-PRRSV SD01-08 PLP2 (385-578) domain and ubiquitin-bound PLP2 DV PLP2-Ub, X-ray diffraction structure determination and analysis at 2.30 A and 2.85 A resolution, respectively
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
purified amino acids (1588-1880) PLP2 domain of nsp3 of SADS-CoV in complex with ubiquitin (Ub), sitting drop vapor diffusion technique using a reservoir solution containing 0.1 M MES, pH 6.5, 0.1 M CaCl2, and 16% PEG 20000, at 16°C for 2 weeks, X-ray diffraction structure determination and analysis at 1.67-1.72 A resolution, structure modelling
-
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C1651A
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
C1651A
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
-
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
T312A/I313V/I353R
C1729A
the mutant shows reduced interferon antagonistic activity compared to that of the wild type enzyme
C44S
site-directed mutagenesis of the active site residue, a catalytically inactive mutant. The reciprocal interactions between Ub and PEDV PLP2 are not disrupted by the C44S mutation
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
C112S
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
D269A
-
site-directed mutagenesis, the mutant shows reduced activity and altered substrate specificity compared to wild-type
D98A
-
site-directed mutagenesis, the mutant shows reduced activity and altered substrate specificity compared to wild-type
F83A
-
site-directed mutagenesis, the mutant shows reduced activity and altered substrate specificity compared to wild-type
H256A
-
site-directed mutagenesis, the mutant shows reduced activity and altered substrate specificity compared to wild-type
N99A
-
site-directed mutagenesis, the mutant shows reduced activity and altered substrate specificity compared to wild-type
W102A
-
site-directed mutagenesis, the mutant shows reduced activity and altered substrate specificity compared to wild-type
Y257A
-
site-directed mutagenesis, the mutant shows reduced activity and altered substrate specificity compared to wild-type
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
additional information
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
-
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
additional information
two residues (Asp195 and Asn196) are deleted to form a PEDV PLP2 mutant, DELTA195-196, the mutant displays reduced DUB activity compared to wild-type PEDV PLP2. The D195-196 mutant also exhibits decreased proteolytic activity on the substrate with the SARSCoV nsp2j3 site but enhanced activity on the substrate with the PEDV nsp2j3 site. Deletion of aa 195 and 196 of PEDV PLP2 decreases the Km toward the substrate with the PEDV nsp2j3 site. Thus, shortened BL2 may result in an enclosed S4 subsite that contributes to a higher substrate binding affinity
additional information
site-directed mutagenesis of PRRSV DV PLP2(385-578)
additional information
porcine reproductive and respiratory syndrome virus isolate Pig/United States/SD 01-08/2001
-
site-directed mutagenesis of PRRSV DV PLP2(385-578)
-
additional information
-
structural identification of recombinant SADS papain-like protease 2 (PLP2) domain of nsp3. Generation of a truncated mutant DELTAN49. Substrate specificities of mutant enzymes compared to the wild-type, overview
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
-
thermolabil, significantly reduced activity after incubation at temperatures higher than 37°C for 30 min
40 - 80
after 10 incubation, the enzyme shows 100% activity between 40 and 55°C, about 97% activity at 60°C, about 65% activity at 70°C, 50% activity at 72°C, about 25% activity at 75°C, and no activity at 80°C
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
GST resin column chromatography, Mono Q column chromatography, and Superdex 75 gel filtration
Ni-NTA column chromatography, Superdex 75 gel filtration, and Source 15Q column chromatography
purified to homogeneity by hydrophobic interaction and anion exchange chromatography
-
recombinant His-tagged PLP2 domain (residues 1616-1945) from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, dialysis, and gel filtration
recombinant His6-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3), the secretion tag is removed and the purification continued by nickel affinity chromatography, gel filtration, and ultrafiltration
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cloned into modified version of the pBacPAK8/His2 vector and expressed in insect cells Sf9
-
cloning of the PLP2 domain originating from PEDV polyprotein 1a, consisting of residues 1616-1945, sequence comparisons, recombinant expression of His6-tagged PLP2 domain in Escherichia coli strain BL21(DE3) from plasmid pET-15b
expressed in Escherichia coli BL21(DE3) cells
expressed in HEK-293T cells
recombinant expression of C-terminally His6-tagged wild-type and mutant enzymes, with a secretion tag, in Escherichia coli strain BL21(DE3)
recombinant expression of the catalytic domain of PEDV PLP2, amino acid (aa) residues 1686 to 1922 of the PEDV polyprotein
recombinant expression of wild-type and mutant C-terminally V5-tagged PRRSV DV PLP2s (amino acid 386-578) from pACNR1185 vector in IFN-deficient BHK-21 cells. For trans cleavage assays, HEK-293T cells are transfected with a combination of pcDNA3.1 plasmids encoding GFP, myc-nsp2C3-HA, and the various PLP2-V5 constructs
vaccinia-T1-mediated expression of a cDNA clone encoding the MHV PLP2 domain
-
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
medicine
drug development
-
the enzyme is an attractive antiviral drug target because it is essential for coronaviral replication. Targeting the enzyme with antiviral drugs may have an advantage in not only inhibiting viral replication but also inhibiting the dysregulation of signaling cascades in infected cells that may lead to cell death in surrounding, uninfected cells
drug development
coronaviral papain-like proteases (PLpros) are attractive targets for antiviral drug development
drug development
-
coronaviral proteases, including main proteases and papain-like proteases (PLP), are attractive antiviral targets because of their essential roles in polyprotein processing and thus viral maturation
medicine
-
PLpro is an important target for development of antiviral drugs that would inhibit viral replication and reduce mortality associated with outbreaks of SARS-CoV
medicine
-
viral strategy to modulate the host cell ubiquitination machinery to its advantage
medicine
-
the enzyme is a potential targets for antiviral drug development
medicine
vaccination of Shetland mares, either with deubiquitinase DUB-positive or DUB-negative recombinant equine arteritis virus. Upon challenge with the virulent KY84 strain of equine arteritis virus, both vaccine viruses proved to be replication competent in vivo. The DUB-negative virus provides a similar degree of protection against clinical disease as its DUB-positive parental counterpart. A possible improvement due to inactivation of PLP2 DUB activity could not be detected under these experimental conditions
medicine
-
PLpro is an important target for development of antiviral drugs that would inhibit viral replication and reduce mortality associated with outbreaks of SARS-CoV
-
medicine
-
viral strategy to modulate the host cell ubiquitination machinery to its advantage
-
medicine
-
vaccination of Shetland mares, either with deubiquitinase DUB-positive or DUB-negative recombinant equine arteritis virus. Upon challenge with the virulent KY84 strain of equine arteritis virus, both vaccine viruses proved to be replication competent in vivo. The DUB-negative virus provides a similar degree of protection against clinical disease as its DUB-positive parental counterpart. A possible improvement due to inactivation of PLP2 DUB activity could not be detected under these experimental conditions
-
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Teng, H.; Pinon, J.D.; Weiss, S.R.
Expression of murine coronavirus recombinant papain-like proteinase: efficient cleavage is dependent on the lengths of both the substrate and the proteinase polypeptide
J. Virol.
73
2658-2666
1999
Murine coronavirus
brenda
Kanjanahaluethai, A.; Baker, S.C.
Identification of mouse hepatitis virus papain-like proteinase 2 activity
J. Virol.
74
7911-7921
2000
Murine coronavirus
brenda
Han, Y.S.; Chang, G.G.; Juo, C.G.; Lee, H.J.; Yeh, S.H.; Hsu, J.T.; Chen, X.
Papain-like protease 2 (PLP2) from severe acute respiratory syndrome coronavirus (SARS-CoV): expression, purification, characterization, and inhibition
Biochemistry
44
10349-10359
2005
Alphacoronavirus, Alphacoronavirus SARS-CoV
brenda
Kanjanahaluethai, A.; Baker, S.C.
Coronavirus papain-like endopeptidases
Handbook of Proteolytic Enzymes (Barrett, A. J. , Rawlings, N. D. , Woessner, J. F. , eds. )Academic Press
2
1265-1269
2004
Alphacoronavirus
-
brenda
Barretto, N.; Jukneliene, D.; Ratia, K.; Chen, Z.; Mesecar, A.D.; Baker, S.C.
The papain-like protease of severe acute respiratory syndrome coronavirus has deubiquitinating activity
J. Virol.
79
15189-15198
2005
Alphacoronavirus, Alphacoronavirus SARS-CoV
brenda
Lindner, H.A.; Fotouhi-Ardakani, N.; Lytvyn, V.; Lachance, P.; Sulea, T.; Menard, R.
The papain-like protease from the severe acute respiratory syndrome coronavirus is a deubiquitinating enzyme
J. Virol.
79
15199-15208
2005
Alphacoronavirus, Alphacoronavirus SARS-CoV
brenda
Ratia, K.; Saikatendu, K.S.; Santarsiero, B.D.; Barretto, N.; Baker, S.C.; Stevens, R.C.; Mesecar, A.D.
Severe acute respiratory syndrome coronavirus papain-like protease: structure of a viral deubiquitinating enzyme
Proc. Natl. Acad. Sci. USA
103
5717-5722
2006
Alphacoronavirus, Alphacoronavirus SARS-CoV
brenda
Ziebuhr, J.; Schelle, B.; Karl, N.; Minskaia, E.; Bayer, S.; Siddell, S.G.; Gorbalenya, A.E.; Thiel, V.
Human coronavirus 229E papain-like proteases have overlapping specificities but distinct functions in viral replication
J. Virol.
81
3922-3932
2007
Human coronavirus 229E
brenda
Chen, Z.; Wang, Y.; Ratia, K.; Mesecar, A.D.; Wilkinson, K.D.; Baker, S.C.
Proteolytic processing and deubiquitinating activity of papain-like proteases of human coronavirus NL63
J. Virol.
81
6007-6018
2007
Human coronavirus NL63
brenda
Chaudhuri, R.; Tang, S.; Zhao, G.; Lu, H.; Case, D.A.; Johnson, M.E.
Comparison of SARS and NL63 papain-like protease binding sites and binding site dynamics: inhibitor design implications
J. Mol. Biol.
414
272-288
2011
Human coronavirus NL63
brenda
Wang, G.; Chen, G.; Zheng, D.; Cheng, G.; Tang, H.
PLP2 of mouse hepatitis virus A59 (MHV-A59) targets TBK1 to negatively regulate cellular type I interferon signaling pathway
PLoS ONE
6
e17192
2011
Murine hepatitis virus
brenda
Sun, L.; Yang, Y.; Liu, D.; Xing, Y.; Chen, X.; Chen, Z.
Deubiquitinase activity and regulation of antiviral innate immune responses by papain-like proteases of human coronavirus NL63
Prog. Biochem. Biophys.
37
871-880
2010
Human coronavirus NL63
-
brenda
Chou, C.Y.; Lai, H.Y.; Chen, H.Y.; Cheng, S.C.; Cheng, K.W.; Chou, Y.W.
Structural basis for catalysis and ubiquitin recognition by the severe acute respiratory syndrome coronavirus papain-like protease
Acta Crystallogr. Sect. D
70
572-581
2014
Severe acute respiratory syndrome-related coronavirus (P0C6U8), Severe acute respiratory syndrome-related coronavirus
brenda
Baez-Santos, Y.M.; St John, S.E.; Mesecar, A.D.
The SARS-coronavirus papain-like protease: structure, function and inhibition by designed antiviral compounds
Antiviral Res.
115
21-38
2015
Severe acute respiratory syndrome-related coronavirus
brenda
Kong, L.; Shaw, N.; Yan, L.; Lou, Z.; Rao, Z.
Structural view and substrate specificity of papain-like protease from avian infectious bronchitis virus
J. Biol. Chem.
290
7160-7168
2015
infectious bronchitis virus (P0C6Y1)
brenda
Xing, Y.; Chen, J.; Tu, J.; Zhang, B.; Chen, X.; Shi, H.; Baker, S.C.; Feng, L.; Chen, Z.
The papain-like protease of porcine epidemic diarrhea virus negatively regulates type I interferon pathway by acting as a viral deubiquitinase
J. Gen. Virol.
94
1554-1567
2013
porcine epidemic diarrhea virus (P0C6Y4)
brenda
Dutta, S.; Dattagupta, J.K.; Biswas, S.
Enhancement of proteolytic activity of a thermostable papain-like protease by structure-based rational design
PLoS ONE
8
e62619
2013
Tabernaemontana divaricata (P83654), Tabernaemontana divaricata
brenda
van Kasteren, P.B.; Bailey-Elkin, B.A.; James, T.W.; Ninaber, D.K.; Beugeling, C.; Khajehpour, M.; Snijder, E.J.; Mark, B.L.; Kikkert, M.
Deubiquitinase function of arterivirus papain-like protease 2 suppresses the innate immune response in infected host cells
Proc. Natl. Acad. Sci. USA
110
E838-E847
2013
equine arteritis virus (P19811)
brenda
Chu, H.F.; Chen, C.C.; Moses, D.C.; Chen, Y.H.; Lin, C.H.; Tsai, Y.C.; Chou, C.Y.
Porcine epidemic diarrhea virus papain-like protease 2 can be noncompetitively inhibited by 6-thioguanine
Antiviral Res.
158
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