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Information on EC 3.4.22.B79 - nsP2 protease
for references in articles please use BRENDA:EC3.4.22.B79preliminary BRENDA-supplied EC number
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EC Tree
3.4.22.B79 nsP2 proteaseSpecify your search results
Word Map
- 3.4.22.B79
- polyproteins
- viruses
- alphavirus
-
chikungunya
-
replicase
-
sindbis
-
chikv
- nsp1
-
semliki
-
subgenomic
-
positive-stranded
-
venezuelan
-
hp-prrsv
-
papain-like
-
noncytopathic
-
plus-stranded
-
positive-sense
-
minus-strand
- analysis
-
3c-like
- drug development
-
autoprotease
- medicine
The enzyme appears in viruses and cellular organisms
Reaction Schemes
the enzymes processes the alphavirus nonstructural polyprotein (nsP1234). The enzyme from Venezuelan equine encephalitis virus shwos a preferens for Gly or Als in position P1', Ala or Cys in P1, and Gly in P2
Synonyms
nonstructural protein 2, nonstructural polyprotein, nsp2 protease, nsp2 protein, nsp2pro, ns polyprotein, 
more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
nonstructural protein 2
nsP2 protease
nsp2pro
p39 nsp2 protease
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
the enzymes processes the alphavirus nonstructural polyprotein (nsP1234). The enzyme from Venezuelan equine encephalitis virus shwos a preferens for Gly or Als in position P1', Ala or Cys in P1, and Gly in P2
-
-
-
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
4-(4-dimethylaminophenyl-azo)benzoyl-DRAGGYIFSE-Edans + H2O
4-(4-dimethylaminophenyl-azo)benzoyl-DRAGG + YIFSE-Edans
4-[[4-(dimethylamino)phenyl]-azo]benzoyl-DELRLDRAGGYIFSS-Edans + H2O
4-[[4-(dimethylamino)phenyl]-azo]benzoyl-DELRLDRAGG + YIFSS-Edans
4-[[4-(dimethylamino)phenyl]-azo]benzoyl-LDRAGGYI-Edans + H2O
4-[[4-(dimethylamino)phenyl]-azo]benzoyl-LDRAGG + YI-Edans
DABCYL-Arg-Ala-Gly-Gly-Tyr-Ile-Phe-Ser-(Glu-EDANS) + H2O
DABCYL-Arg-Ala-Gly-Gly + Tyr-Ile-Phe-Ser-(Glu-EDANS)
-
-
-
?
Sindbis virus core protein + H2O
Hydrolyzed Sindbis core protein
-
-
-
-
?
thioredoxin fusion protein + H2O
?
-
fusion protein is cleaved with greater efficiency by nsp2pro than the original MBP-NusG-His6 substrate with the shorter linker
-
-
?
Venezuelan equine encephalitis virus p1/p2 + H2O
?
-
-
-
?
Venezuelan equine encephalitis virus p3/p4 + H2O
?
-
-
-
?
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp) + H2O
2-(N-methylamino)benzoyl-AGA + GIIETk(Dnp)
-
-
-
-
?
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp) + H2O
2-(N-methylamino)benzoyl-AGA + GIIETk(Dnp)
-
corresponds to cleavage site P1/2 of the polyprotein
-
-
?
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp) + H2O
2-(N-methylamino)benzoyl-AGA + GIIETk(Dnp)
Chikungunya virus ECSA E1:226V
-
-
-
-
?
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp) + H2O
2-(N-methylamino)benzoyl-AGC + GIIETk(Dnp)
-
-
-
-
?
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp) + H2O
2-(N-methylamino)benzoyl-AGC + GIIETk(Dnp)
-
corresponds to cleavage site P2/3 of the polyprotein
-
-
?
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp) + H2O
2-(N-methylamino)benzoyl-AGC + GIIETk(Dnp)
Chikungunya virus ECSA E1:226V
-
-
-
-
?
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp) + H2O
2-(N-methylamino)benzoyl-AGG + GIIETk(Dnp)
-
-
-
-
?
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp) + H2O
2-(N-methylamino)benzoyl-AGG + GIIETk(Dnp)
-
corresponds to cleavage site P3/4 of the polyprotein
-
-
?
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp) + H2O
2-(N-methylamino)benzoyl-AGG + GIIETk(Dnp)
Chikungunya virus ECSA E1:226V
-
-
-
-
?
4-(4-dimethylaminophenyl-azo)benzoyl-DRAGGYIFSE-Edans + H2O
4-(4-dimethylaminophenyl-azo)benzoyl-DRAGG + YIFSE-Edans
-
-
-
?
4-(4-dimethylaminophenyl-azo)benzoyl-DRAGGYIFSE-Edans + H2O
4-(4-dimethylaminophenyl-azo)benzoyl-DRAGG + YIFSE-Edans
Chikungunya virus S27-African prototype
-
-
-
?
4-[[4-(dimethylamino)phenyl]-azo]benzoyl-DELRLDRAGGYIFSS-Edans + H2O
4-[[4-(dimethylamino)phenyl]-azo]benzoyl-DELRLDRAGG + YIFSS-Edans
-
-
-
?
4-[[4-(dimethylamino)phenyl]-azo]benzoyl-DELRLDRAGGYIFSS-Edans + H2O
4-[[4-(dimethylamino)phenyl]-azo]benzoyl-DELRLDRAGG + YIFSS-Edans
Chikungunya virus ECSA
-
-
-
?
4-[[4-(dimethylamino)phenyl]-azo]benzoyl-LDRAGGYI-Edans + H2O
4-[[4-(dimethylamino)phenyl]-azo]benzoyl-LDRAGG + YI-Edans
peptide representing the 1/2 site of the polyprotein. Substrate is processed by nsP2, but the reaction velocity cannot be saturated
-
-
?
4-[[4-(dimethylamino)phenyl]-azo]benzoyl-LDRAGGYI-Edans + H2O
4-[[4-(dimethylamino)phenyl]-azo]benzoyl-LDRAGG + YI-Edans
Chikungunya virus ECSA
peptide representing the 1/2 site of the polyprotein. Substrate is processed by nsP2, but the reaction velocity cannot be saturated
-
-
?
additional information
?
-
-
chikungunya nsP2 protease possesses different substrate specificity to the canonical alphavirus nsP2 polyprotein cleavage specificity
-
-
?
additional information
?
-
protease readily cleaves GFP-10:5-Trx substrates containing short P10-P5' sequences originating from the 1/2 and 3/4 cleavage sites of the polyprotein, but not from the 2/3 site. Enzyme prefers the 3/4 substrate for cleavage in trans
-
-
?
additional information
?
-
Chikungunya virus ECSA
protease readily cleaves GFP-10:5-Trx substrates containing short P10-P5' sequences originating from the 1/2 and 3/4 cleavage sites of the polyprotein, but not from the 2/3 site. Enzyme prefers the 3/4 substrate for cleavage in trans
-
-
?
additional information
?
-
Chikungunya virus ECSA E1:226V
-
chikungunya nsP2 protease possesses different substrate specificity to the canonical alphavirus nsP2 polyprotein cleavage specificity
-
-
?
additional information
?
-
-
the catalytic dyad is composed of Cys-481 and His-558
-
-
?
additional information
?
-
-
enzyme is critically involved in development of cytopathic effect. Cytotoxic effect of enzyme is due to its ability to cause transcriptional shutoff
-
-
?
additional information
?
-
-
after negative-strand synthesis, the ns protein appears to irreversibly change conformation and forms mature replication complexes, in spite of the lack of ns polyprotein cleavage. Complete processing of the ns polyprotein is not an absolute prerequisite for Sindbis virus replication. Inability of the viruses with unprocessed polyprotein to productively replicate in the interferon-competent cells and in the cells of mosquito origin is an additional, important factor in ns polyprotein cleavage development. It leads to the release of nsP2 protein, which plays a critical role in inhibiting the cellular antiviral response
-
-
?
additional information
?
-
-
recombinant Sindbis viruses encoding nsP2/GFP chimeric protein are capable of growth in tissue culture and interfering with cellular functions. GFP insertion after the eighth amino acid of nsP2 in the SIN/nsP2GFP/8 virus blocks the processing of one of the cleavage sites. In the SIN/nsP2GFP/472 virus, the GFP insertion causes the formation process for nsP2/GFP to pass through an additional step of processing, in which the intermediate product of a higher molecular weight is initially formed and then processed to a final form of nsP2/GFP
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
enzyme is critically involved in development of cytopathic effect. Cytotoxic effect of enzyme is due to its ability to cause transcriptional shutoff
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
-
stimulation with substrates 2-(N-methylamino)benzoyl-AGCGIIETk(Dnp) and 2-(N-methylamino)benzoyl-AGGGIIETk(Dnp), inhibition with substrate 2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(5E)-6-(4-methoxyphenyl)-4-oxo-N-(2-phenylethyl)hex-5-enamide
topographical peptidomimetic, binds covalently leading to permanent enzyme inactivation via Michael adduct formation between the alpha/beta-unsaturated ketone functionality and the active site. 100% inhibition at 0.059 mg/ml, EC50 for cell-based assay 0.0089 mg/ml
(5E)-N-benzyl-4-oxo-6-phenylhex-5-enamide
topographical peptidomimetic, binds covalently leading to permanent enzyme inactivation via Michael adduct formation between the alpha/beta-unsaturated ketone functionality and the active site. 100% inhibition at 0.068 mg/ml, EC50 for cell-based assay 0.0088 mg/ml
E64d
inhibitor binds beneath a beta-hairpin at the interface of the SAM MTase and protease domains
Mg2+
-
stimulation with substrates 2-(N-methylamino)benzoyl-AGCGIIETk(Dnp) and 2-(N-methylamino)benzoyl-AGGGIIETk(Dnp), inhibition with substrate 2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)
PMSF
-
PMSF does not affect activity when using 2-(N-methylamino)benzoyl-AGAGIIETk(Dnp) as a substrate. With 2-(N-methylamino)benzoyl-AGAGIIETk(Dnp), PMSF shows no effect on truncated protease and 30% inhibition of full-length NSP2
Zinc acetate
almost complete inhibition at 2 mM, also significantly reduces the virus load in Vero cells
Cu2+
-
strong inhibition with substrate 2-(N-methylamino)benzoyl-AGCGIIETk(Dnp)
glycerol
-
activity is reduced by approximately 20fold in the presence of 5% glycerol
glycerol
activity is reduced by approximately 20fold in the presence of 5% glycerol
additional information
-
not inhibitory: leupeptin, E-64. Poor inhibitors: chymostatin, PMSF; not inhibitory to full-length enzyme: NaCl up to 2 M, but 30-40% inhibition at 1 M with truncated protease
-
additional information
not inhibitory: PMSF, trypsin protease inhibitor I, pepstatin, EDTA
-
additional information
-
not inhibitory: PMSF, trypsin protease inhibitor I, pepstatin, EDTA
-
additional information
-
dithiothreitol and tris (2-carboxyethyl) phosphine hydrochloride have no discernable effect on the activity up to 5 mM. The enzyme is able to tolerate up to 10 mM of beta-mercaptoethanol
-
additional information
nsp2pro can tolerate EDTA up to 10 mM with very little effect. Dithiothreitol and tris (2-carboxyethyl) phosphine hydrochloride have no discernable effect on the activity up to 5 mM. The enzyme is able to tolerate up to 10 mM of beta-mercaptoethanol
-
additional information
-
nsp2pro can tolerate EDTA up to 10 mM with very little effect. Dithiothreitol and tris (2-carboxyethyl) phosphine hydrochloride have no discernable effect on the activity up to 5 mM. The enzyme is able to tolerate up to 10 mM of beta-mercaptoethanol
-
additional information
E64c, the carboxylic acid form of the E64d ester, does not inhibit the nsP2 protease
-
additional information
-
E64c, the carboxylic acid form of the E64d ester, does not inhibit the nsP2 protease
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
NaCl has relatively little effect on enzymatic activity up to 200 mM
-
additional information
NaCl has relatively little effect on enzymatic activity up to 200 mM
-
additional information
-
NaCl has relatively little effect on enzymatic activity up to 200 mM
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0025
4-[[4-(dimethylamino)phenyl]-azo]benzoyl-DELRLDRAGGYIFSS-Edans
30°C, pH not specified in the publication
0.00098
DABCYL-Arg-Ala-Gly-Gly-Tyr-Ile-Phe-Ser-(Glu-EDANS)
pH 8.0, temperature not specified in the publication
0.00023
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)
-
presence of glutathione disulfide, pH 7.5, 37°C
0.00033
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)
-
mutant C478A, pH 7.5, 37°C
0.00041
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)
-
mutant W549F, pH 7.5, 37°C
0.00104
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)
-
mutant S482A, pH 7.5, 37°C
0.00301
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)
-
mutant W549A, pH 7.5, 37°C
0.0066
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)
-
wild-type enzyme, pH 7.5, 37°C
0.0093
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)
-
full-length enzyme, pH 7.5, 37°C
0.0364
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)
-
truncated enzyme, pH 7.5, 37°C
0.00041
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp)
-
mutant W549F, pH 7.5, 37°C
0.00043
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp)
-
presence of glutathione disulfide, pH 7.5, 37°C
0.0007
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp)
-
wild-type enzyme, pH 7.5, 37°C
0.00077
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp)
-
mutant W549A, pH 7.5, 37°C
0.00109
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp)
-
mutant S482A, pH 7.5, 37°C
0.00184
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp)
-
mutant C478A, pH 7.5, 37°C
0.0045
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp)
-
truncated enzyme, pH 7.5, 37°C
0.0099
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp)
-
full-length enzyme, pH 7.5, 37°C
0.00016
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp)
-
presence of glutathione disulfide, pH 7.5, 37°C
0.00058
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp)
-
mutant S482A, pH 7.5, 37°C
0.00072
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp)
-
mutant C478A, pH 7.5, 37°C
0.00076
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp)
-
mutant W549F, pH 7.5, 37°C
0.00086
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp)
-
wild-type enzyme, pH 7.5, 37°C
0.00269
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp)
-
mutant W549A, pH 7.5, 37°C
0.0074
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp)
-
truncated enzyme, pH 7.5, 37°C
0.009
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp)
-
full-length enzyme, pH 7.5, 37°C
0.01
4-(4-dimethylaminophenyl-azo)benzoyl-DRAGGYIFSE-Edans
wild-type, pH not specified in the publication, temperature not specified in the publication
0.029
4-(4-dimethylaminophenyl-azo)benzoyl-DRAGGYIFSE-Edans
mutant N547A, pH not specified in the publication, temperature not specified in the publication
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00052
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)
-
mutant C478A, pH 7.5, 37°C
0.00076
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)
-
mutant W549F, pH 7.5, 37°C
0.00084
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)
-
presence of glutathione disulfide, pH 7.5, 37°C
0.00164
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)
-
mutant S482A, pH 7.5, 37°C
0.0027
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)
-
full-length enzyme, pH 7.5, 37°C
0.0032
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)
-
mutant W549A, pH 7.5, 37°C
0.0033
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)
-
truncated enzyme, pH 7.5, 37°C
0.0046
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)
-
wild-type enzyme, pH 7.5, 37°C
0.0013
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp)
-
mutant W549F, pH 7.5, 37°C
0.00142
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp)
-
presence of glutathione disulfide, pH 7.5, 37°C
0.0021
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp)
-
mutant S482A, pH 7.5, 37°C
0.0024
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp)
-
wild-type enzyme, pH 7.5, 37°C
0.0029
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp)
-
truncated enzyme, pH 7.5, 37°C
0.0031
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp)
-
mutant C478A, pH 7.5, 37°C
0.0034
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp)
-
full-length enzyme, pH 7.5, 37°C
0.0075
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp)
-
mutant W549A, pH 7.5, 37°C
0.00068
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp)
-
presence of glutathione disulfide, pH 7.5, 37°C
0.0011
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp)
-
truncated enzyme, pH 7.5, 37°C
0.0013
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp)
-
mutant W549F, pH 7.5, 37°C
0.0014
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp)
-
mutant S482A, pH 7.5, 37°C
0.0015
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp)
-
mutant C478A, pH 7.5, 37°C
0.0016
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp)
-
wild-type enzyme, pH 7.5, 37°C
0.0017
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp)
-
mutant W549A, pH 7.5, 37°C
0.0019
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp)
-
full-length enzyme, pH 7.5, 37°C
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.072
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)
-
wild-type enzyme, pH 7.5, 37°C
0.091
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)
-
truncated enzyme, pH 7.5, 37°C
0.29
2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)
-
full-length enzyme, pH 7.5, 37°C
0.35
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp)
-
full-length enzyme, pH 7.5, 37°C
0.361
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp)
-
wild-type enzyme, pH 7.5, 37°C
0.65
2-(N-methylamino)benzoyl-AGCGIIETk(Dnp)
-
truncated enzyme, pH 7.5, 37°C
0.15
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp)
-
truncated enzyme, pH 7.5, 37°C
0.179
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp)
-
wild-type enzyme, pH 7.5, 37°C
0.21
2-(N-methylamino)benzoyl-AGGGIIETk(Dnp)
-
full-length enzyme, pH 7.5, 37°C
0.14
4-(4-dimethylaminophenyl-azo)benzoyl-DRAGGYIFSE-Edans
mutant N547A, pH not specified in the publication, temperature not specified in the publication
0.41
4-(4-dimethylaminophenyl-azo)benzoyl-DRAGGYIFSE-Edans
wild-type, pH not specified in the publication, temperature not specified in the publication
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4 - 30
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Venezuelan equine encephalitis virus Trinidad donkey
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
SIN/nsP2GFP/8-specific fusion protein is present in the cytoplasm in large complexes. SIN/nsP2GFP/472 also present
brenda
-
very little amounts of SIN/nsP2GFP/8-specific fusion protein. SIN/nsP2GFP/472 also present
brenda
additional information
-
SIN/nsP2GFP/8-specific fusion protein is present in the cytoplasm in large complexes, and very little is found in the nuclei, nsP2/GFP of SIN/nsP2GFP/472 is distributed both in the cytoplasm and in the nucleus
-
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
-
nsP2 inhibits cellular transcription by inducing rapid degradation of Rpb1, a catalytic subunit of the RNAPII complex. This degradation of Rpb1 is independent of the nsP2-associated protease activity, but, instead, it proceeds through nsP2-mediated Rpb1 ubiquitination. This function of nsP2 depends on the integrity of the helicase and S-adenosylmethionine (SAM)-dependent methyltransferase-like domains, and point mutations in either of these domains abolish Rpb1 degradation
physiological function
nsP2 inhibits cellular transcription by inducing rapid degradation of Rpb1, a catalytic subunit of the RNAPII complex. This degradation of Rpb1 is independent of the nsP2-associated protease activity, but, instead, it proceeds through nsP2-mediated Rpb1 ubiquitination. This function of nsP2 depends on the integrity of the helicase and S-adenosylmethionine (SAM)-dependent methyltransferase-like domains, and point mutations in either of these domains abolish Rpb1 degradation
physiological function
nsP2 inhibits cellular transcription by inducing rapid degradation of Rpb1, a catalytic subunit of the RNAPII complex. This degradation of Rpb1 is independent of the nsP2-associated protease activity, but, instead, it proceeds through nsP2-mediated Rpb1 ubiquitination. This function of nsP2 depends on the integrity of the helicase and S-adenosylmethionine (SAM)-dependent methyltransferase-like domains, and point mutations in either of these domains abolish Rpb1 degradation
physiological function
-
nsP2 is either directly or indirectly involved in the RNA encapsidation process
physiological function
-
a serine that is close to the catalytical dyad is catalytically interchangeable with the dyad cysteine residue. The enzyme retains activity upon alanine replacement of either residue but a replacement of both cysteine and serine residues results in no detectable activity
physiological function
complete elimination of nonstructural proteins nsp1 and nsp2 does not abolish viral viability
physiological function
upon transfection of HeLa cells, 21 differentially regulated (six upregulated, 15 downregulated) spots are observed. Ubiquitin-conjugating enzyme UBE2L3 is downregulated. Transfection of full length UBE2L3 into HEK293T/17 cells prior to CHIKV infection reduces levels of infection but does not alter RNA genome levels
physiological function
-
complete elimination of nonstructural proteins nsp1 and nsp2 does not abolish viral viability
-
physiological function
Chikungunya virus ECSA E1:226V
-
a serine that is close to the catalytical dyad is catalytically interchangeable with the dyad cysteine residue. The enzyme retains activity upon alanine replacement of either residue but a replacement of both cysteine and serine residues results in no detectable activity
-
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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). A6NA54_PRRSV
2473
0
269204
TrEMBL
-
R1AB_CVMA5
Murine coronavirus (strain A59)
7176
14
802596
Swiss-Prot
Secretory Pathway (Reliability: 1)
POLN_EEVVT
2493
0
277887
Swiss-Prot
-
POLN_CHIKS
Chikungunya virus (strain S27-African prototype)
2474
0
275652
Swiss-Prot
-
POLN_EEVVM
2499
2
278684
Swiss-Prot
-
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
cytotoxic functions of of enzyme are determined by the integrity of the carboxy-terminal peptide rather than its protease activity and depend on the presence of protein in a free form
?
x * 71000, nsP2 protease GST-fusion protein with a dual (His6-GST) affinity tag
?
Chikungunya virus S27-African prototype
-
x * 37000, SDS-PAGE
-
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
nonstructural proteins nsP1-4 are produced as a single polyprotein, and processing of the polyprotein occurs in a highly regulated manner. The P2/3 cleavage site is located at the base of a narrow cleft and is not readily accessible. The nsP2 protease active site is over 40 A away from the P2/3 cleavage site, supporting a trans cleavage mechanism
side-chain modification
-
in virus-infected cells, nsP2 can be glutathionylated at residues C175, C214, C313, C462, C698, C755. The glutathionylation of nsP2 impacts on the protease activity
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
homology model of nsP2 protein based on the crystal structure of the nsP2 protein of Venezuelan equine encephalitis virus and proposal of the the pharmacophore features that must be present in an inhibitor of nsP2 protease
molecular dynamics simulation and virtual screening of inhibitors based on PDB entry 3TRK leads to identification of top hit compounds, together with the five potential binding pockets of the nsP2 protease. Pocket 4 in the N-terminal domain of the nsP2 protease has been identified as the active site by the presence of catalytic residues, Cys1013 and His1083
molecular dynamics simulations and comparison with papain. The active site scaffold is the same in both the proteases. The two structurally identical segments in both the proteases show considerable difference in terms of their mobility
to 2.59 A resolution. Protein consists of an N-terminal protease subdomain and a C-terminal methyltransferase subdomain. The substrate binding cleft is present at the interface of two subdomains. Access to the active site and substrate binding cleft is blocked by a flexible interdomain loop. This loop contains His548, the catalytic residue, and Trp549 and Asn547, the residues predicted to bind substrate
hanging drop vapor diffusion method, using 12%(w/v) PEG 8000, 10%(v/v) ethylene glycol, 100 mM HEPES pH 7.5
-
structure of nonstructural protein P23 in a precleavage form. The proteins form an extensive interface and nsP3 creates a ring structure that encircles nsP2. The P2/3 cleavage site is located at the base of a narrow cleft and is not readily accessible. The nsP2 protease active site is over 40 A away from the P2/3 cleavage site, supporting a trans cleavage mechanism. nsP3 contains a previously uncharacterized protein fold with a zinc-coordination site. Known mutations in nsP2 that result in formation of noncytopathic viruses or a temperature sensitive phenotype cluster at the nsP2/nsP3 interface
at 2.45 A resolution. Belongs to space group P212121. N-terminal domain (Asp468 to Asn603) contains the catalytic dyad formed by Cys477 and His546, organized in a protein fold. C-terminal domain (Arg604 to Ser793) contributes to substrate recognition and regulates the structure of the substrate binding cleft
combination of molecular dynamics simulations with structural studies. The catalytic mechanism of the nsP2 protease appears similar to the papain-like cysteine proteases, with the conserved catalytic dyad forming a thiolate-imidazolium ion pair in the nsP2-activated state. Substrate binding likely stabilizes this ion pair. Protease residues His510, Ser511, His546, and Lys706 are critical for cleavage site recognition. Structural determinants of substrate specificity that recognize features common to all three cleavage sites within the viral polyprotein are strongly conserved among alphaviruses. Contacts between S2/P2 and S3/P3 residues illustrate preserved binding motifs such as the ubiquitous P2 glycine interaction with Trp547 and hydrogen bonding between P2 and His510
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C478A
S482A
W479A
mutation completely abolishes RNA replication trans-replication systems and abolishes the rescue of infectious virus from CHIKV RNA transcripts
W549A
-
mutation involved in structural stability of the loop that contains the catalytic histidine residue
W549F
-
mutation involved in structural stability of the loop that contains the catalytic histidine residue
C478A
Chikungunya virus ECSA
-
residue Cys478 in the active site of CHIKV nsP2 is indispensable for polyprotein P1234 processing. Mutation completely abolishes RNA replication trans-replication systems and abolishes the rescue of infectious virus from CHIKV RNA transcripts
-
W479A
Chikungunya virus ECSA
-
mutation completely abolishes RNA replication trans-replication systems and abolishes the rescue of infectious virus from CHIKV RNA transcripts
-
C478A
Chikungunya virus ECSA E1:226V
-
significantly less activity than wild type for the 2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)substrate
-
S482A
Chikungunya virus ECSA E1:226V
-
significantly less activity than wild type for the 2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)substrate
-
W549A
Chikungunya virus ECSA E1:226V
-
mutation involved in structural stability of the loop that contains the catalytic histidine residue
-
W549F
Chikungunya virus ECSA E1:226V
-
mutation involved in structural stability of the loop that contains the catalytic histidine residue
-
C478A
Chikungunya virus S27-African prototype
-
mutation in active site, loss of activity
-
N547A
Chikungunya virus S27-African prototype
-
mutation leads to three-fold increase in Km value
-
N600D
-
significantly impaired activity. Slower growth rate and smaller bacterial mass as well as a reduced expression level of the corresponding soluble Pro39. Results in preparates with lower degree of purity and shows a tendency to aggregate
N605D
-
significantly impaired activity. Slower growth rate and smaller bacterial mass as well as a reduced expression level of the corresponding soluble Pro39. Results in preparates with lower degree of purity and shows a tendency to aggregate
C481G
-
mutation in C-terminal protease domain, abolishes catalytic activity, and is lethal
C481R
-
mutation in C-terminal protease domain, abolishes catalytic activity, and is lethal
C481S
-
mutation in C-terminal protease domain, abolishes catalytic activity, and is lethal
C525R
-
mutation in C-terminal protease domain, abolishes catalytic activity, and is lethal
H558A
-
mutation in C-terminal protease domain, abolishes catalytic activity, and is lethal
H558Q
-
mutation in C-terminal protease domain, abolishes catalytic activity, and is lethal
H558Y
-
mutation in C-terminal protease domain, abolishes catalytic activity, and is lethal
H709R
-
mutation in C-terminal protease domain, abolishes catalytic activity, and is lethal
P726A
-
the mutant exhibits similar growth characteristics to the wild type BR-XJ160 in cultured cells, including cytopathic effects, plaque morphology and growth kinetics
P726L
-
the mutant shows no cytopathic effects or plaques after six passages through BHK-21 cells, although expression of XJ-160 virus-specific protein is detectable, the mutant produces no lethality or morbidity in suckling mice
P726S
-
the mutant shows reduced growth capacity in cultured cells and mouse brain, and intermediate neurovirulence
P726V
-
the mutant exhibits similar growth characteristics to the wild type BR-XJ160 in cultured cells, including cytopathic effects, plaque morphology and growth kinetics
Y559A
-
mutation in C-terminal protease domain, abolishes catalytic activity, and is lethal
G17V
-
mutation causes an increase in infectous viral titer, variants become cytopathic for both BHK-21 and Vero cells
K480A
mutation leads to a 9fold decrease in kcat and kcat/Km. K480 likely enhances the nucleophilicity of the Cys residue
K706A
SAM MTase domain mutation, increases Km 4.5fold to 500 microM
N475A
N545A
mutation within the beta-hairpin, lightly but not significantly increases kcat and Km
N545D
-
mutation causes an increase in infectous viral titer, variants become cytopathic for both BHK-21 and Vero cells
Q471L
-
mutation causes an increase in infectous viral titer, variants become cytopathic for both BHK-21 and Vero cells
R662A
mutation leads to 16fold decreases in kcat/Km
R662K
mutation leads to 16fold decreases in kcat/Km
T5A
-
mutation causes an increase in infectous viral titer, variants become cytopathic for both BHK-21 and Vero cells
T5I
-
mutation causes an increase in infectous viral titer, variants become cytopathic for both BHK-21 and Vero cells
V3A
-
mutation causes an increase in infectous viral titer, variants become cytopathic for both BHK-21 and Vero cells
K480A
Venezuelan equine encephalitis virus Trinidad donkey
-
mutation leads to a 9fold decrease in kcat and kcat/Km. K480 likely enhances the nucleophilicity of the Cys residue
-
K706A
Venezuelan equine encephalitis virus Trinidad donkey
-
SAM MTase domain mutation, increases Km 4.5fold to 500 microM
-
N475A
R662A
Venezuelan equine encephalitis virus Trinidad donkey
-
mutation leads to 16fold decreases in kcat/Km
-
R662K
Venezuelan equine encephalitis virus Trinidad donkey
-
mutation leads to 16fold decreases in kcat/Km
-
S701A
Venezuelan equine encephalitis virus Trinidad donkey
-
mutation leads to a 17fold increase in Km
-
additional information
C478A
residue Cys478 in the active site of CHIKV nsP2 is indispensable for polyprotein P1234 processing. Mutation completely abolishes RNA replication trans-replication systems and abolishes the rescue of infectious virus from CHIKV RNA transcripts
C478A
-
significantly less activity than wild type for the 2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)substrate
S482A
mutation has almost no negative effect on the protease activity
S482A
-
significantly less activity than wild type for the 2-(N-methylamino)benzoyl-AGAGIIETk(Dnp)substrate
N475A
mutation leads to a 24fold reduction in kcat/Km, and the conformation of this residue does not change after inhibition. Residue N475 forms the base of the P1 binding site and likely orients the substrate for nucleophilic attack or plays a role in product release
N475A
mutation of a conserved motif residue, produces a self-inhibited state in which the N-terminal residues flipp into the substrate-binding cleft. Mutation results in a 70fold decrease in kcat/Km
N475A
Venezuelan equine encephalitis virus Trinidad donkey
-
mutation leads to a 24fold reduction in kcat/Km, and the conformation of this residue does not change after inhibition. Residue N475 forms the base of the P1 binding site and likely orients the substrate for nucleophilic attack or plays a role in product release
-
N475A
Venezuelan equine encephalitis virus Trinidad donkey
-
mutation of a conserved motif residue, produces a self-inhibited state in which the N-terminal residues flipp into the substrate-binding cleft. Mutation results in a 70fold decrease in kcat/Km
-
additional information
-
preparation of both full length and a truncated protease domain from the C-terminus of the nsP2 protein. The protease domain alone has different properties compared with the full length nsP2 protease
additional information
Chikungunya virus ECSA E1:226V
-
preparation of both full length and a truncated protease domain from the C-terminus of the nsP2 protein. The protease domain alone has different properties compared with the full length nsP2 protease
-
additional information
-
mutants with deletions and/or mutations at the N-terminal border of the nsp2 PLP2-DUB domain. A 23-amino-acid deletion of amino acids 402 to 424 of the ORF1a-encoded protein largely abolishes the inhibitory effect of nsp2 on ubiquitin-like protein ISG15 production and conjugation, but no viable recombinant virus is recovered. A 19-amino-acid deletion of amino acids 402 to 420, in combination with downstream point mutation S465A, partially relieves the ISG15 antagonist function and yields a viable recombinant virus
additional information
-
SIN/2V/389 virus, has GFP insertion after aa 389 of nsP3 and a single-point mutation leading to replacement of glycine by valine in the P2 position of the cleavage site between nsP2 and nsP3. Blocks polyprotein processing
additional information
-
ns polyprotein cleavage mutants of Sindbis virus differ from the Sindbis virus/GFP variant in their ability to inhibit cellular translation and transcription. The nsP2/nsP3 cleavage site mutant replicates in BHK-21 cells almost as efficiently as the cleavage competent Sindbis virus/GFP. In the case of the 1V2V ns polyprotein mutant, only one additional substitution in the nsP4 protein sequence is required to strongly increase RNA replication (but not the transcription of the subgenomic RNA) to the wild-type level. Ns polyprotein cleavage mutants induce a strong interferon-alpha/beta response
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
42
-
10 min, 50.4% residual activity for wild-type, 53% for mutant C478A, 50.4% for mutant S482A, 52.9% for mutant W549A, 54% for mutant W549F
30
activity decreases dramatically at temperatures above 30°C
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ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70°C, 20 mM HEPES buffer, pH 7.4, 200 mM NaCl, 20% glycerol, 0.1% Tween 20, 1 mM DTT, 1 mM EDTA, 12 months
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
fusion proteins purified by immobilized metal affinity chromatography, to homogeneity
fusion proteins purified by immobilized metal affinity chromatography, to homogeneity
-
fusion proteins purified by immobilized metal affinity chromatography, to homogeneity
-
fusion proteins purified by immobilized metal affinity chromatography, to homogeneity
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA coding for nsP2pro (residues Met457-Cys794) amplified and cloned into vector pETBlue1 T7. Expression in Tuner DE3 (pLacI) Escherichia coli cells
expressed initially as HisMBP fusion proteins in Escherichia coli BL21(DE3) CodonPlus-RIL cells
expression in Escherichia coli
expression in Escherichia coli. Proteins are expressed as inclusion bodies under culturing at 37°C, and only partially expressed in a soluble form at 22°C
-
GFP-encoding DNA fragment cloned into the nsP2 gene by using a transposon-based approach. The entire library of the recombinant nsP2/GFP genes transferred into wild-type Sindbis virus Toto1101 genome. SIN/nsP2GFP/8 and SIN/nsP2GFP/472 expressed in BHK-21 cells
-
GFP-encoding DNA fragment randomly cloned into the nsP2 gene. Entire library of the recombinant nsP2/GFP genes transferred into wild-type SINV Toto1101 genome. BHK-21 cells infected with SIN/nsP2GFP/8 and with both packaged replicons and SIN/nsP2GFP/472 virus
-
the gene that encodes a double-mutant IBV nsp2 N-terminal domain (residues 9-393 of the polyprotein, with mutations Q132L and L270F) is expressed in Escherichia coli BL21(DE3) cells
-
expressed initially as HisMBP fusion proteins in Escherichia coli BL21(DE3) CodonPlus-RIL cells
-
expressed initially as HisMBP fusion proteins in Escherichia coli BL21(DE3) CodonPlus-RIL cells
-
expressed initially as HisMBP fusion proteins in Escherichia coli BL21(DE3) CodonPlus-RIL cells
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
drug development
medicine
additional information
-
nsP2/GFP is capable of efficient functioning in Sindbis virus replication complexes that can synthesize RNA and, ultimately, produce virus at a level comparable to that of wild-type Sindbis virus. GFP inserted into nsP2 is accessible to specific antibodies and capable of functioning as an efficient tag for the isolation of protein complexes formed during Sindbis virus replication
analysis
assay for quantitative measurement of Nsp2 protease activity based on a substrate fusion protein consisting of eGFP and Gaussia luciferase linked together by a small peptide containing a Nsp2 protease cleavage sequence. The expression of the substrate protein in cells along with recombinant Nsp2 protease results in cleavage of the substrate protein resulting in extracellular release of free Gaussia luciferase
analysis
nsP2 protease-based cell free high throughput screening assay
analysis
Venezuelan equine encephalitis virus Mena II
-
assay for quantitative measurement of Nsp2 protease activity based on a substrate fusion protein consisting of eGFP and Gaussia luciferase linked together by a small peptide containing a Nsp2 protease cleavage sequence. The expression of the substrate protein in cells along with recombinant Nsp2 protease results in cleavage of the substrate protein resulting in extracellular release of free Gaussia luciferase
-
drug development
-
alphavirus nsp2pro proteases are not very useful tools for the removal of affinity tags from recombinant proteins although they do remain promising therapeutic targets for the treatment of a variety of diseases
drug development
-
alphavirus nsp2pro proteases are not very useful tools for the removal of affinity tags from recombinant proteins although they do remain promising therapeutic targets for the treatment of a variety of diseases
drug development
alphavirus nsp2pro proteases are not very useful tools for the removal of affinity tags from recombinant proteins although they do remain promising therapeutic targets for the treatment of a variety of diseases
medicine
the nsp2pro N-terminal domain is a novel cysteine protease fold. the C-terminal domain displays structural similarity to S-adenosyl-L-methionine-dependent RNA methyltransferases. This structure will significantly aid drug discovery and development efforts to combat Venezuelan equine encephalitis alphavirus and related viruses
medicine
-
SINV nsP2 is an important factor in viral RNA replication and modification of cell biology
medicine
-
ubiquitin-like protein ISG15 overexpression inhibits porcine reproductive and respiratory syndrome virus replication in cell culture and the antiviral activity of interferon is reduced by inhibition of ISG15 conjugation. Nonstructural protein nsp2 is a key factor in counteracting the antiviral function of ISG15
medicine
minimal linear Nsp2 B cell epitopes, 188ELSDDSNRPV197, 42HLKRYSPPAE51, and 54CGWHCISA61, are identified by the monoclonal antibodies 4A12, 4G8, and 8H11, respectively. 42HLKRYSPPAE51 and 188ELSDDSNRPV197 are located separately in hypervariable region 1 and hypervariable region 2 of Nsp2. 54CGWHCISA61 is located in the PL2 region, which is highly conserved in all arteriviruses. 54CGWHCISA61 is located in the inner region of the expected 3D structure of Nsp2
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Strauss, E.G.; De Groot, R.J.; Levinson, R.; Strauss, J.H.
Identification of the active site residues in the nsP2 proteinase of Sindbis virus
Virology
191
932-940
1992
Sindbis virus
brenda
Garmashova, N.; Gorchakov, R.; Frolova, E.; Frolov, I.
Sindbis virus nonstructural protein nsP2 is cytotoxic and inhibits cellular transcription
J. Virol.
80
5686-5696
2006
Sindbis virus
brenda
Golubtsov, A.; Kaeaeriaeinen, L.; Caldentey, J.
Characterization of the cysteine protease domain of Semliki Forest virus replicase protein nsP2 by in vitro mutagenesis
FEBS Lett.
580
1502-1508
2006
Semliki forest virus
brenda
Atasheva, S.; Gorchakov, R.; English, R.; Frolov, I.; Frolova, E.
Development of Sindbis viruses encoding nsP2/GFP chimeric proteins and their application for studying nsP2 functioning
J. Virol.
81
5046-5057
2007
Sindbis virus
brenda
Russo, A.T.; White, M.A.; Watowich, S.J.
The crystal structure of the Venezuelan equine encephalitis alphavirus nsP2 protease
Structure
14
1449-1458
2006
Venezuelan equine encephalitis virus (P27282)
brenda
Gorchakov, R.; Frolova, E.; Sawicki, S.; Atasheva, S.; Sawicki, D.; Frolov, I.
A new role for ns polyprotein cleavage in Sindbis virus replication
J. Virol.
82
6218-6231
2008
Sindbis virus
brenda
Mayuri, L.; Geders, T.W.; Smith, J.L.; Kuhn, R.J.
Role for conserved residues of sindbis virus nonstructural protein 2 methyltransferase-like domain in regulation of minus-strand synthesis and development of cytopathic infection
J. Virol.
82
7284-7297
2008
Sindbis virus
brenda
Zhang, D.; Toezser, J.; Waugh, D.S.
Molecular cloning, overproduction, purification and biochemical characterization of the p39 nsp2 protease domains encoded by three alphaviruses
Protein Expr. Purif.
64
89-97
2009
Semliki forest virus, Sindbis virus, Venezuelan equine encephalitis virus (P27282), Venezuelan equine encephalitis virus
brenda
Yang, A.; Wei, L.; Zhao, W.; Xu, Y.; Rao, Z.
Expression, crystallization and preliminary X-ray diffraction analysis of the N-terminal domain of nsp2 from avian infectious bronchitis virus
Acta Crystallogr. Sect. F
65
788-790
2009
infectious bronchitis virus
brenda
Zhu, W.Y.; Fu, S.H.; Wang, J.L.; He, Y.; Tang, Q.; Liang, G.D.
Effects of the nsP2-726 Pro mutation on infectivity and pathogenesis of Sindbis virus derived from a full-length infectious cDNA clone
Virus Res.
142
204-207
2009
Sindbis virus
brenda
Russo, A.T.; Malmstrom, R.D.; White, M.A.; Watowich, S.J.
Structural basis for substrate specificity of alphavirus nsP2 proteases
J. Mol. Graph. Model.
29
46-53
2010
Venezuelan equine encephalitis virus (P27282), Venezuelan equine encephalitis virus
brenda
Nguyen, P.; Yu, H.; Keller, P.
Identification of chikungunya virus nsP2 protease inhibitors using structure-base approaches
J. Mol. Graph. Model.
57
1-8
2015
Chikungunya virus (Q8JUX6), Chikungunya virus, Chikungunya virus S27 (Q8JUX6)
brenda
Singh, K.; Kirubakaran, P.; Nagarajan, S.; Sakkiah, S.; Muthusamy, K.; Velmurgan, D.; Jeyakanthan, J.
Homology modeling, molecular dynamics, e-pharmacophore mapping and docking study of Chikungunya virus nsP2 protease
J. Mol. Model.
18
39-51
2012
Chikungunya virus (Q8JUX6), Chikungunya virus, Chikungunya virus S27 (Q8JUX6)
brenda
Sun, Z.; Li, Y.; Ransburgh, R.; Snijder, E.J.; Fang, Y.
Nonstructural protein 2 of porcine reproductive and respiratory syndrome virus inhibits the antiviral function of interferon-stimulated gene 15
J. Virol.
86
3839-3850
2012
porcine reproductive and respiratory syndrome virus
brenda
Akhrymuk, I.; Kulemzin, S.V.; Frolova, E.I.
Evasion of the innate immune response: the Old World alphavirus nsP2 protein induces rapid degradation of Rpb1, a catalytic subunit of RNA polymerase II
J. Virol.
86
7180-7191
2012
Sindbis virus, Semliki forest virus (P08411), Chikungunya virus (Q8JUX6), Chikungunya virus
brenda
Kim, D.Y.; Atasheva, S.; Frolova, E.I.; Frolov, I.
Venezuelan equine encephalitis virus nsP2 protein regulates packaging of the viral genome into infectious virions
J. Virol.
87
4202-4213
2013
Venezuelan equine encephalitis virus
brenda
Shin, G.; Yost, S.A.; Miller, M.T.; Elrod, E.J.; Grakoui, A.; Marcotrigiano, J.
Structural and functional insights into alphavirus polyprotein processing and pathogenesis
Proc. Natl. Acad. Sci. USA
109
16534-16539
2012
Sindbis virus (P03317)
brenda
Bi, C.; Shao, Z.; Li, J.; Weng, C.
Identification of novel epitopes targeting non-structural protein 2 of PRRSV using monoclonal antibodies
Appl. Microbiol. Biotechnol.
103
2689-2699
2019
porcine reproductive and respiratory syndrome virus (A6NA54), porcine reproductive and respiratory syndrome virus
brenda
Hu, X.; Compton, J.R.; Leary, D.H.; Olson, M.A.; Lee, M.S.; Cheung, J.; Ye, W.; Ferrer, M.; Southall, N.; Jadhav, A.; Morazzani, E.M.; Glass, P.J.; Marugan, J.; Legler, P.M.
Kinetic, mutational, and structural studies of the Venezuelan equine encephalitis virus nonstructural protein 2 cysteine protease
Biochemistry
55
3007-3019
2016
Venezuelan equine encephalitis virus (P27282), Venezuelan equine encephalitis virus, Venezuelan equine encephalitis virus Trinidad donkey (P27282)
brenda
Compton, J.R.; Mickey, M.J.; Hu, X.; Marugan, J.J.; Legler, P.M.
Mutation of Asn-475 in the Venezuelan equine encephalitis virus nsP2 cysteine protease leads to a self-inhibited state
Biochemistry
56
6221-6230
2017
Venezuelan equine encephalitis virus (P27282), Venezuelan equine encephalitis virus Trinidad donkey (P27282)
brenda
Saisawang, C.; Kuadkitkan, A.; Smith, D.R.; Ubol, S.; Ketterman, A.J.
Glutathionylation of chikungunya nsP2 protein affects protease activity
Biochim. Biophys. Acta
1861
106-111
2017
Chikungunya virus
brenda
El-labbad, E.M.; Ismail, M.A.; Abou Ei Ella, D.A.; Ahmed, M.; Wang, F.; Barakat, K.H.; Abouzid, K.A.
Discovery of novel peptidomimetics as irreversible CHIKV NsP2 protease inhibitors using quantum mechanical-based ligand descriptors
Chem. Biol. Drug Des.
86
1518-1527
2015
Chikungunya virus (C8YZ72), Chikungunya virus, Chikungunya virus 899 (C8YZ72)
brenda
Ramakrishnan, C.; Kutumbarao, N.H.V.; Suhitha, S.; Velmurugan, D.
Structure-function relationship of Chikungunya nsP2 protease A comparative study with papain
Chem. Biol. Drug Des.
89
772-782
2017
Chikungunya virus (Q8JUX6), Chikungunya virus, Chikungunya virus S27-African prototype (Q8JUX6)
brenda
Narwal, M.; Singh, H.; Pratap, S.; Malik, A.; Kuhn, R.J.; Kumar, P.; Tomar, S.
Crystal structure of chikungunya virus nsP2 cysteine protease reveals a putative flexible loop blocking its active site
Int. J. Biol. Macromol.
116
451-462
2018
Chikungunya virus (Q8JUX6), Chikungunya virus, Chikungunya virus S27-African prototype (Q8JUX6)
brenda
Hurst-Hess, K.R.; Kuo, L.; Masters, P.S.
Dissection of amino-terminal functional domains of murine coronavirus nonstructural protein 3
J. Virol.
89
6033-6047
2015
Murine coronavirus (P0C6X9), Murine coronavirus A59 (P0C6X9)
brenda
Ramphan, S.; Khongwichit, S.; Saisawang, C.; Kovanich, D.; Ketterman, A.J.; Ubol, S.; Auewarakul, P.; Roytrakul, S.; Smith, D.R.; Kuadkitkan, A.
Ubiquitin-conjugating enzyme E2 L3 is downregulated by the chikungunya virus nsP2 protease
Proteomics Clin. Appl.
12
e1700020
2018
Chikungunya virus (A0A0E3MZW7), Chikungunya virus
brenda
Saisawang, C.; Saitornuang, S.; Sillapee, P.; Ubol, S.; Smith, D.; Ketterman, A.
Chikungunya nsP2 protease is not a papain-like cysteine protease and the catalytic dyad cysteine is interchangeable with a proximal serine
Sci. Rep.
5
17125
2015
Chikungunya virus, Chikungunya virus ECSA E1:226V
brenda
Rausalu, K.; Utt, A.; Quirin, T.; Varghese, F.S.; Zusinaite, E.; Das, P.K.; Ahola, T.; Merits, A.
Chikungunya virus infectivity, RNA replication and non-structural polyprotein processing depend on the nsP2 proteases active site cysteine residue
Sci. Rep.
6
37124
2016
Chikungunya virus (Q1W368), Chikungunya virus ECSA (Q1W368)
brenda
Saha, A.; Acharya, B.; Priya, R.; Tripathi, N.; Shrivastava, A.; Rao, M.; Kesari, P.; Narwal, M.; Tomar, S.; Bhagyawant, S.; Parida, M.; Dash, P.
Development of nsP2 protease based cell free high throughput screening assay for evaluation of inhibitors against emerging Chikungunya virus
Sci. Rep.
8
10831
2018
Chikungunya virus (C7S7A0), Chikungunya virus
brenda
Campos-Gomez, J.; Ahmad, F.; Rodriguez, E.; Saeed, M.F.
A novel cell-based assay to measure activity of Venezuelan equine encephalitis virus nsP2 protease
Virology
496
77-89
2016
Venezuelan equine encephalitis virus (Q9WJC7), Venezuelan equine encephalitis virus, Venezuelan equine encephalitis virus Mena II (Q9WJC7)
brenda
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