Information on EC 3.4.22.B14 - papain-like proteinase 1

for references in articles please use BRENDA:EC3.4.22.B14
Word Map on EC 3.4.22.B14
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Select one or more organisms in this record:

The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.4.22.B14
preliminary BRENDA-supplied EC number
RECOMMENDED NAME
GeneOntology No.
papain-like proteinase 1
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
papain-like proteinase 1 is responsible for cleavages located at the N-terminus of the replicase polyprotein
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
strains 229E, NL, OC43 and HKU1
SwissProt
Manually annotated by BRENDA team
severe acute respiratory syndrome coronavirus, Urbani strain
-
-
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
4-[[4-(dimethylamino)phenyl]azo]benzoic acid-MYNKMGGGDKTVSF-(5-[(2-aminoethyl)amino]naphthalene-1-sulfonic acid) amide + H2O
?
show the reaction diagram
coronavirus nonstructural protein 1 + H2O
?
show the reaction diagram
-
-
-
-
?
coronavirus nonstructural protein 2 + H2O
?
show the reaction diagram
-
-
-
-
?
coronavirus nonstructural protein 3 + H2O
?
show the reaction diagram
-
-
-
-
?
L-Arg-L-Leu-L-Arg-Gly-Gly-7-amido-4-methylcoumarin + H2O
L-Arg-L-Leu-L-Arg-Gly-Gly + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
ORF 1a polyprotein + H2O
?
show the reaction diagram
ORF 1a polyprotein + H2O
nsp1 + nsp2 + nsp3
show the reaction diagram
p28
?
show the reaction diagram
-
-
-
-
?
p65
?
show the reaction diagram
-
-
-
-
?
ubiquitin-7-amido-4-methylcoumarin + H2O
ubiquitin + 7-amino-4-methylcoumarin
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ORF 1a polyprotein + H2O
?
show the reaction diagram
p28
?
show the reaction diagram
-
-
-
-
?
p65
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2,6-dimethyl-N-[(R)-1-(2-naphthyl)ethyl]benzamide
-
-
2,N-dimethyl-N-[(R)-1-(2-naphthyl)ethyl]benzamide
-
-
2-methoxy-N-[(R)-1-(2-naphthyl)ethyl]benzamide
-
-
2-methoxymethyl-5-nitrobenzoic acid methyl ester
-
-
2-methyl-N-[(R)-1-(1-naphthyl)ethyl]benzamide
-
-
2-methyl-N-[1-(naphthalen-2-yl)ethyl]benzamide
-
-
3-methoxy-N-[(R)-1-(2-naphthyl)ethyl]benzamide
-
-
3-methyl-N-[(R)-1-(2-naphthyl)ethyl]benzamide
-
-
4-amino-N-[(R)-1-(1-naphthyl)ethyl]benzamide
-
-
4-amino-N-[(R)-1-(2-naphthyl)ethyl]benzamide
-
-
4-methoxy-N-[(R)-1-(2-naphthyl)ethyl]benzamide
-
-
4-methyl-N-[(R)-1-(2-naphthyl)ethyl]benzamide
-
-
5-amino-2-methoxymethyl-N-[1-methyl-1-(1-naphthyl)ethyl]benzamide
-
-
5-amino-2-methyl-N-[(R)-1-(1-naphthyl)ethyl]benzamide
-
-
5-amino-2-methyl-N-[1-methyl-1-(1-naphthyl)ethyl]benzamide
-
-
5-cyano-2-methyl-N-[1-methyl-1-(1-naphthyl)ethyl]benzamide
-
-
5-iodo-2-methyl-N-[1-methyl-1-(1-naphthyl)ethyl]benzamide
-
-
5-methylamino-2-methyl-N-[(R)-1-(1-naphthyl)ethyl]benzamide
-
-
5-N-acetylamino-2-methyl-N-[(R)-1-(1-naphthyl)ethyl]benzamide
-
-
5-N-tert-butoxycarbonylmethylamino-2-methyl-N'-[(R)-1-(1-naphthyl)ethyl]benzamide
-
-
E-64d
-
membrane-permeable do the irreversible cysteine proteinase inhibitor E-64 blocks cleavage of p65 in vivo
leupeptin
-
blocks the ability of PLP1 to cleave p28 in vitro but not in vivo due to permeability and toxicity issues
N-methyl-5-methylamino-2-methyl-N'-[(R)-1-(1-naphthyl)ethyl]benzamide
-
-
ZnCl2
-
blocks the ability of PLP1 to cleave p28 in vitro but not in vivo due to permeability and toxicity issues
additional information
-
not inhibited by 2-hydroxy-N-[(R)-1-(2-naphthyl)ethyl]benzamide, 4-N'-tert-butoxycarbonylamino-N-[(R)-1-(2-naphthyl)ethyl]-benzamide, 2-methyl-N-[1-(2-naphthyl)propyl]benzamide, and 2-methyl-N-[1-(2-naphthyl)benzyl]benzamide
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0121
2,6-dimethyl-N-[(R)-1-(2-naphthyl)ethyl]benzamide
SARS coronavirus
-
in 50 mM HEPES, pH 7.5
0.0226
2,N-dimethyl-N-[(R)-1-(2-naphthyl)ethyl]benzamide
SARS coronavirus
-
in 50 mM HEPES, pH 7.5
0.09
2-methoxy-N-[(R)-1-(2-naphthyl)ethyl]benzamide
SARS coronavirus
-
in 50 mM HEPES, pH 7.5
0.0014
2-methoxymethyl-5-nitrobenzoic acid methyl ester
SARS coronavirus
-
in 50 mM HEPES, pH 7.5
0.0023
2-methyl-N-[(R)-1-(1-naphthyl)ethyl]benzamide
SARS coronavirus
-
in 50 mM HEPES, pH 7.5
0.0087
2-methyl-N-[1-(naphthalen-2-yl)ethyl]benzamide
SARS coronavirus
-
in 50 mM HEPES, pH 7.5
0.0135
3-methoxy-N-[(R)-1-(2-naphthyl)ethyl]benzamide
SARS coronavirus
-
in 50 mM HEPES, pH 7.5
0.0148
3-methyl-N-[(R)-1-(2-naphthyl)ethyl]benzamide
SARS coronavirus
-
in 50 mM HEPES, pH 7.5
0.0248
4-amino-N-[(R)-1-(1-naphthyl)ethyl]benzamide
SARS coronavirus
-
in 50 mM HEPES, pH 7.5
0.0461
4-amino-N-[(R)-1-(2-naphthyl)ethyl]benzamide
SARS coronavirus
-
in 50 mM HEPES, pH 7.5
0.149
4-methoxy-N-[(R)-1-(2-naphthyl)ethyl]benzamide
SARS coronavirus
-
in 50 mM HEPES, pH 7.5
0.0291
4-methyl-N-[(R)-1-(2-naphthyl)ethyl]benzamide
SARS coronavirus
-
in 50 mM HEPES, pH 7.5
0.0052
5-amino-2-methoxymethyl-N-[1-methyl-1-(1-naphthyl)ethyl]benzamide
SARS coronavirus
-
in 50 mM HEPES, pH 7.5
0.00056
5-amino-2-methyl-N-[(R)-1-(1-naphthyl)ethyl]benzamide
SARS coronavirus
-
in 50 mM HEPES, pH 7.5
0.00056
5-amino-2-methyl-N-[1-methyl-1-(1-naphthyl)ethyl]benzamide
SARS coronavirus
-
in 50 mM HEPES, pH 7.5
0.0111
5-cyano-2-methyl-N-[1-methyl-1-(1-naphthyl)ethyl]benzamide
SARS coronavirus
-
in 50 mM HEPES, pH 7.5
0.0027
5-iodo-2-methyl-N-[1-methyl-1-(1-naphthyl)ethyl]benzamide
SARS coronavirus
-
in 50 mM HEPES, pH 7.5
0.00046
5-methylamino-2-methyl-N-[(R)-1-(1-naphthyl)ethyl]benzamide
SARS coronavirus
-
in 50 mM HEPES, pH 7.5
0.00264
5-N-acetylamino-2-methyl-N-[(R)-1-(1-naphthyl)ethyl]benzamide
SARS coronavirus
-
in 50 mM HEPES, pH 7.5
0.0048
5-N-tert-butoxycarbonylmethylamino-2-methyl-N'-[(R)-1-(1-naphthyl)ethyl]benzamide
SARS coronavirus
-
in 50 mM HEPES, pH 7.5
0.0013
N-methyl-5-methylamino-2-methyl-N'-[(R)-1-(1-naphthyl)ethyl]benzamide
SARS coronavirus
-
in 50 mM HEPES, pH 7.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
reaction is significantly more efficient at 22°C than when carried out at 30°C
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method, using 0.1-0.18 M (NH4)2SO4, 0.1 M MES (pH 6.5), and 30% (w/v) PEG 5000, at 19°C
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Ni-NTA column chromatography and Superdex 75 gel filtration
recombinant enzyme
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloned into plasmids under T7 promoter control and cotransfected into HeLa-MHVR cells infected with recombinant vaccinia virus
-
expressed in Escherichia coli
-
expressed in Escherichia coli Rosetta (DE3)pLysS cells
expression in Escherichia coli by using a T7 RNA polymerase promoter system or as a maltose-binding protein fusion protein. With both overexpression systems the recombinant PLP-1 exhibits trans cleavage activity. When PLP-1 is expressed as a polypeptide that includes additional viral sequences at the carboxyl terminus of the predicted PLP-1 domain, a fivefold increase in proteolytic activity is observed