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Information on EC 3.4.22.46 - L-peptidase and Organism(s) Foot-and-mouth disease virus and UniProt Accession P03305
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3.4.22.46 L-peptidaseSpecify your search results
Word Map
- 3.4.22.46
- polyproteins
- viruses
- enterovirus
- rhinovirus
-
capsid
- poliovirus
- picornavirus
-
serotypes
- coxsackievirus
- vp3
- picornaviridae
-
encephalomyocarditis
-
papain-like
- rupintrivir
-
3c-like
-
poliovirus-infected
-
anti-ev71
-
cloven-hoofed
-
coxsackie
-
fmdv-infected
- aphthovirus
-
seneca
- 3clpro
- drug development
The taxonomic range for the selected organisms is: Foot-and-mouth disease virus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
3c protease, 3cpro, leader protease, l proteinase, nsp1alpha, lab protein, p1a protein, fmdv 3cpro, leader peptidase nisp, leader peptidase b, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
sLbpro
during infection, isoform Lbpro removes six residues from its own C-terminus, generating sLbpro
Eukaryotic signal peptidase
-
-
-
-
Eukaryotic signal proteinase
-
-
-
-
L proteinase
Leader peptidase
-
-
-
-
Leader peptide hydrolase
-
-
-
-
Leader proteinase
Lpro
Peptidase, signal
-
-
-
-
Prokaryotic leader peptidase
-
-
-
-
Prokaryotic signal peptidase
-
-
-
-
Prokaryotic signal proteinase
-
-
-
-
Propeptidase
-
-
-
-
Proteinase, eukaryotic signal
-
-
-
-
Proteinase, signal
-
-
-
-
Signal peptidase
-
-
-
-
Signalase
-
-
-
-
L proteinase
-
-
-
-
Leader proteinase
-
-
-
-
Leader proteinase
-
-
Lpro
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
934238-57-0
-
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
eukaryotic initiation factor eIF4G + H2O
?
in intermolecular cleavage on polyprotein substrates, isoform Lbpro is unaffected by P1 or P1' substitutions and processes a substrate containing nine eIF4GI cleavage site residues whereas isoform sLbpro fails to cleave the eIF4GI containing substrate and cleaves appreciably more slowly on mutated substrates
-
-
?
SFANLGRTTL + H2O
SFANLG + RTTL
poor substrate for both isoforms Lbpro and sLbpro
-
-
?
VQRKLGAAGQ + H2O
VQRKLG + AAGQ
isoform sLbpro cleaves this substrate better than isoform Lbpro
-
-
?
VQRKLGRAGQ + H2O
VQRKLG + RAGQ
isoform sLbpro cleaves this substrate better than isoform Lbpro
-
-
?
VQRKLKGAGQ + H2O
VQRKLK + GAGQ
isoform sLbpro cleaves this substrate better than isoform Lbpro
-
-
?
VQRKLKRAGQ + H2O
VQRKLK + RAGQ
isoform sLbpro cleaves this substrate better than isoform Lbpro
-
-
?
Abz-KLKGAGQ-EDDnp + H2O
Abz-KLK + GAGQ-EDDnp
-
hydrolysis of FRET peptides
-
-
?
eukaryotic initiation factor 4G + H2O
?
-
Lbpro cleaves two homologues of the host cell protein. Lbpro possesses specific binding sites at the non-prime side from S1 down to S7
-
-
?
Val-Gln-Arg-Lys-Leu-Lys-4-methylcoumarin 7-amide + H2O
Val-Gln-Arg-Lys-Leu-Lys + 7-amino-4-methylcoumarin
-
the substrate corresponds to the six C-terminal amino acids of the leader protein
-
?
eukaryotic initiation factor eIF4GI + H2O
?
-
eukaryotic host cell protein substrate, cleavage prevents the synthesis of host cellular protein from capped cellular mRNAs, while the viral RNA is tsill translated initiating from an internal ribosome entry site
-
-
?
eukaryotic initiation factor eIF4GI + H2O
?
-
eukaryotic host cell protein substrate, recognition/cleavage site is ANLG*RTTL
-
-
?
eukaryotic initiation factor eIF4GI + H2O
?
-
eukaryotic host cell protein substrate, cleavage between residues G674 and R675, the enzyme binds to substrate residues 640-669 and interacts with C133 and residues 183-195, interaction analysis of enzyme with recombinant peptide fragments, reduced binding with mutated peptides K643A, K646A, and R650A overview
-
-
?
eukaryotic initiation factor eIF4GII + H2O
?
-
eukaryotic host cell protein substrate, cleavage prevents the synthesis of host cellular protein from capped cellular mRNAs, while the viral RNA is tsill translated initiating from an internal ribosome entry site
-
-
?
eukaryotic initiation factor eIF4GII + H2O
?
-
eukaryotic host cell protein substrate, recognition/cleavage site is LNVG*SRRS, but not ADFG*RQTP
-
-
?
eukaryotic initiation factor eIF4GII + H2O
?
-
eukaryotic host cell protein substrate
-
-
?
eukaryotic translation initiation factor eIF4GI + H2O
?
-
eukaryotic host cell protein substrate, cleavage causes the rapid inhibition of cellular cap-dependent protein synthesis
-
-
?
eukaryotic translation initiation factor eIF4GI + H2O
?
-
eukaryotic host cell protein substrate, cleavage causes the rapid inhibition of cellular cap-dependent protien synthesis
-
-
?
eukaryotic translation initiation factor eIF4GI + H2O
?
-
eukaryotic host cell protein substrate
-
-
?
eukaryotic translation initiation factor eIF4GI + H2O
?
-
eukaryotic host cell protein substrate, activity of 3Cpro and Lpro with wild-type and mutant substrate, overview, the highly specific 3Cpro cleavage site is located at the small 40-amino-acid region of the protein
-
-
?
foot-and-mouth disease leader protein + H2O
?
-
cis and trans cleavage activity at the L/P1 junction
-
-
?
foot-and-mouth disease leader protein + H2O
?
-
similar to other papain-like proteinases the enzyme possesses the catalytic cysteine and histidine residues, however the catalytic asparagine has been replaced by an aspartate. The interaction between the histidine and aspartate is exposed to solvent, as the tryptophan residues are missing. The cleavage site is between its own C-terminus and the N-terminus of VP4
-
-
?
RNA helicase LGP2 + H2O
?
-
LGP2 cleavage by the Leader protease of aphthoviruses may represent an antagonistic mechanism for immune evasion
-
-
?
additional information
?
-
-
no hydrolysis of Phe-Arg-4-methylcoumarin 7-amide, Val-Lue-Lys-4-methylcoumarin 7-amide, classical papain substrates, or Ser-Phe-Ala-Asn-Leu-Gly-4-methylcoumarin 7-amide, corresponding to the N-terminal portion of the eIF4G cleavage site
-
-
?
additional information
?
-
-
the enzyme inhibits the immediate-early induction of beta interferon mRNA and blocks the host innate immune response by inhibition of IFN-induction of double-stranded RNA-dependent protein kinase R, 2',5'-oligoadenylate synthase, and Mx1 mRNAs in host porcine cells
-
-
?
additional information
?
-
-
elIF4GI cleavage site mapping
-
-
?
additional information
?
-
-
substrate recognition and cleavage site specificity, overview
-
-
?
additional information
?
-
-
the enzyme is synthesized as part of a large polyprotein LbproVP4VP, from which it releases itself by highly efficient self-processing between its C- and N-terminus of the subsequent protein VP4, recognition of the sequence QRKLK*GAGQ, specificity at the P2, Leu, and P3 positions, including S3 subsite preferring Lys or Asn, and comparison with other papain-like enzymes, no activity when Pro is at P2 position and with type I collagen, overview, residues P99, P100, L143, A149, and L178 determine the specificity of the S2 binding pocket
-
-
?
additional information
?
-
-
the leader protease, Lbpro, performs the initial cleavage by freeing itself from the growing polypeptide chain. Lbpro is not only one of the smallest papain-like cysteine peptidases but also one of the most specific. It has high prime side specificity at least down to the S' 5 site. It can still however cleave between both K-G and G-R pairs
-
-
?
additional information
?
-
-
the enzyme typically recognise the alternating positions of the side chains along the polypeptide sequence that are characteristic of an extended backbone conformation, and this serves to place the scissile bond in the correct orientation at the active site. Significant conformational adaptation by the enzyme is important for substrate recognition
-
-
?
additional information
?
-
-
the enzyme cleaves itself off the nascent viral polyprotein
-
-
?
translation initiation factor eIF4G + H2O
additional information
-
-
-
-
-
?
translation initiation factor eIF4G + H2O
additional information
-
-
-
-
-
?
translation initiation factor eIF4G + H2O
additional information
-
-
-
-
-
?
translation initiation factor eIF4G + H2O
additional information
-
-
-
characterization of cleavage products, primary cleavage of rabbit reticulocyte eIF-4-gamma occurs between Gly479-Arg480, complete proteolysis after 12 h
?
translation initiation factor eIF4G + H2O
additional information
-
-
very rapid reaction
-
-
?
translation initiation factor eIF4G + H2O
additional information
-
-
i.e. p220
-
-
?
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
eukaryotic initiation factor eIF4G + H2O
?
in intermolecular cleavage on polyprotein substrates, isoform Lbpro is unaffected by P1 or P1' substitutions and processes a substrate containing nine eIF4GI cleavage site residues whereas isoform sLbpro fails to cleave the eIF4GI containing substrate and cleaves appreciably more slowly on mutated substrates
-
-
?
eukaryotic initiation factor 4G + H2O
?
-
Lbpro cleaves two homologues of the host cell protein. Lbpro possesses specific binding sites at the non-prime side from S1 down to S7
-
-
?
RNA helicase LGP2 + H2O
?
-
LGP2 cleavage by the Leader protease of aphthoviruses may represent an antagonistic mechanism for immune evasion
-
-
?
eukaryotic initiation factor eIF4GI + H2O
?
-
eukaryotic host cell protein substrate, cleavage prevents the synthesis of host cellular protein from capped cellular mRNAs, while the viral RNA is tsill translated initiating from an internal ribosome entry site
-
-
?
eukaryotic initiation factor eIF4GI + H2O
?
-
eukaryotic host cell protein substrate, recognition/cleavage site is ANLG*RTTL
-
-
?
eukaryotic initiation factor eIF4GII + H2O
?
-
eukaryotic host cell protein substrate, cleavage prevents the synthesis of host cellular protein from capped cellular mRNAs, while the viral RNA is tsill translated initiating from an internal ribosome entry site
-
-
?
eukaryotic initiation factor eIF4GII + H2O
?
-
eukaryotic host cell protein substrate, recognition/cleavage site is LNVG*SRRS, but not ADFG*RQTP
-
-
?
eukaryotic translation initiation factor eIF4GI + H2O
?
-
eukaryotic host cell protein substrate, cleavage causes the rapid inhibition of cellular cap-dependent protein synthesis
-
-
?
eukaryotic translation initiation factor eIF4GI + H2O
?
-
eukaryotic host cell protein substrate, cleavage causes the rapid inhibition of cellular cap-dependent protien synthesis
-
-
?
foot-and-mouth disease leader protein + H2O
?
-
cis and trans cleavage activity at the L/P1 junction
-
-
?
foot-and-mouth disease leader protein + H2O
?
-
similar to other papain-like proteinases the enzyme possesses the catalytic cysteine and histidine residues, however the catalytic asparagine has been replaced by an aspartate. The interaction between the histidine and aspartate is exposed to solvent, as the tryptophan residues are missing. The cleavage site is between its own C-terminus and the N-terminus of VP4
-
-
?
additional information
?
-
-
the enzyme inhibits the immediate-early induction of beta interferon mRNA and blocks the host innate immune response by inhibition of IFN-induction of double-stranded RNA-dependent protein kinase R, 2',5'-oligoadenylate synthase, and Mx1 mRNAs in host porcine cells
-
-
?
additional information
?
-
-
the leader protease, Lbpro, performs the initial cleavage by freeing itself from the growing polypeptide chain. Lbpro is not only one of the smallest papain-like cysteine peptidases but also one of the most specific. It has high prime side specificity at least down to the S' 5 site. It can still however cleave between both K-G and G-R pairs
-
-
?
additional information
?
-
-
the enzyme cleaves itself off the nascent viral polyprotein
-
-
?
translation initiation factor eIF4G + H2O
additional information
-
-
-
-
-
?
translation initiation factor eIF4G + H2O
additional information
-
-
-
-
-
?
translation initiation factor eIF4G + H2O
additional information
-
-
-
-
-
?
translation initiation factor eIF4G + H2O
additional information
-
-
-
characterization of cleavage products, primary cleavage of rabbit reticulocyte eIF-4-gamma occurs between Gly479-Arg480, complete proteolysis after 12 h
?
translation initiation factor eIF4G + H2O
additional information
-
-
very rapid reaction
-
-
?
translation initiation factor eIF4G + H2O
additional information
-
-
i.e. p220
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
CA074
-
epoxide-based inhibitor of cysteine proteinases, two-step overall irreversible inhibition, with step one being reversible and step two irreversible
E64
-
epoxide-based inhibitor of cysteine proteinases, two-step overall irreversible inhibition, with step one being reversible and step two irreversible. Extending E64 by addition of the dipeptide R-P to a compound termed E64-R-P-NH2, which irreversibly inhibits Lbpro with a Ki of 30 nM and k4 of 0.01/min, can serve as the basis for design of specific inhibitors of FMDV replication
E64-R-P-NH2
-
extending E64 by addition of the dipeptide R-P to a compound termed E64-R-P-NH2, which irreversibly inhibits Lbpro with a Ki of 30 nM and k4 of 0.01/min, can serve as the basis for design of specific inhibitors of FMDV replication
additional information
-
sensitive to high ionic strength, 50% inactivation by 20 mM NaCl or 10 mM CaCl2
-
trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane
-
i.e. E-64
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0116
CA074
isoform Lbpro, pH and temperature not specified in the publication
0.00003
E64-R-P-NH2
isoform Lbpro, pH and temperature not specified in the publication
additional information
additional information
-
kinetics mechanism of two-step overall irreversible inhibition by cysteinase inhibitors
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
self-processing activity of the enzyme on wild-type and mutant polyproteins, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.2 - 9.8
-
less than 50% of maximal activity above and below, substrate Val-Gln-Arg-Lys-Leu-Lys-4-methylcoumarin 7-amide
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
the L signal is mainly localized to the nuclei of infected cells, while VP1 is detected in the cytoplasm, thereafter the L signal is detected throughout the whole cell. The pattern of L sub-cellular localization of the L mutant viruses is similar to the WT virus, except for a delay in the cytoplasmic L protein signal
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
Lpro is localized to the nucleus of infected cells, and there is a correlation between the translocation of Lpro and the decrease in the amount of nuclear p65/RelA, a subunit of NF-kappa B
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
significant conformational adaptation by the enzyme is important for substrate recognition, specificity differences between 3Cpro from different picornaviruses, overview
physiological function
physiological function
-
foot and mouth disease virus expresses its genetic information as a single polyprotein that is translated from the single-stranded RNA genome. The leader protease, Lbpro, performs the initial cleavage by freeing itself from the growing polypeptide chain. Subsequently, Lbpro cleaves the two homologues of the host cell protein eukaryotic initiation factor 4G, eIF4G. Lbpro possesses specific binding sites at the non-prime side from S1 down to S7
physiological function
-
the leader proteinase, Lpro, acts as an interferon-beta antagonist and inhibits IFN-alpha1/beta promoter activation, poly(I:C)-induced IFN-alpha1/beta mRNA expression, and dsRNA-induced type I interferon transcription by decreasing interferon regulatory factor 3/7 in protein levels. Lpro significantly reduced the transcription of multiple IRF-responsive genes
physiological function
-
the viral RNA genome is translated in the cytoplasm of infected cells as a long polyprotein precursor that is cleaved by virally encoded proteases to release functional proteins needed for the synthesis of new virions. In 10 of 13 cases, 3Cpro performs the cleavages by targeting specific sequences within the polyprotein
physiological function
-
the enzyme inhibits the host innate immune response by the revention of the synthesis of cytokines such as interferons immediately after infection (brought about by specific proteolytic cleavage of the eukaryotic initiation factor 4G) as well as nuclear factor-kappaB cleavage and the deubiquitination of immune signalling molecules
physiological function
-
LGP2 cleavage by the Leader protease of aphthoviruses may represent an antagonistic mechanism for immune evasion
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
-
dimer in solution, determined by NMR-spectroscopy. Dimer can not be dissociated by increasing the ionic strength or by dilution
homodimer
additional information
-
the peptide binding cleft, which contains the active site at its centre, is located at the interface between two beta-barrels. Unusually, picornaviral 3Cpro possess a Cys-His-Asp/Glu catalytic triad at the centre of this cleft, instead of the Ser-His-Asp arrangement of active-site residues
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
-
the enzyme is synthesized as part of a large polyprotein LbproVP4VP2, from which it releases itself by highly efficient self-processing between its C- and N-terminus of the subsequent protein VP4, recognition of the sequence QRKLK*GAGQ, Asp at P3 and Phe at P2 severely compromise the self-processing
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
isoform sLbpro in complex with inhibitor E-64-R-P-NH2, hanging drop vapor diffusion method, using 0.1 M sodium acetate pH 4.8, 0.9 M NaH2PO4 and 1.2 M K2HPO4
crystal structures of LbproC51A, LbproC51A/C133S, sLbproC51A/C133S
-
foot-and-mouth disease virus 3C protease mutant C95K/C142L/C163A complexed with a peptide substrates APAKQLLNFD and APAKELLNFD that spans P5-P5', 1:5.5 molar ratio of enzyme to peptide, 0.05 ml of of 3Cpro solution at 17 mg/ml protein in 100 mM HEPES, pH 7.0, 400 mM NaCl, 1 mM EDTA, 2 mM 2-mercaptoethanol, and 0.01% w/v sodium azide is mixed with 0.007 ml of 30 mM peptide dissolved in the same buffer, yielding a final protein concentration of 14.9 mg/ml, sitting-drop vapour diffusion, room temperature, mixing of 0.001 ml of protein complex solution with 0.003 ml reservoir composed of 40-43% PEG 400, 0.2 M LiSO4 and 0.1 M Tris, pH 8.0 X-ray diffraction structure determination and analysis
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
L143A
self-processes efficiently at the L(pro)/VP4 cleavage site containing P2 phenylalanine, self-processing at the eIF4GII sequence Asp-Phe-Gly-Arg-Gln-Thr is improved but shows more-extensive aberrant processing
L143M
does not self-process efficiently at the L(pro)/VP4 cleavage site containing P2 phenylalanine
C95K/C142L/C163A
-
the C-terminally truncated, catalytically inactive mutant has wild-type binding activity but remains soluble at purified protein concentrations in excess of 10 mg/ml
C95K/C142S/C163A
-
C-terminally truncated, catalytically inactive form of the type A10FMDV 3Cpro
L200F
-
the mutant is impaired in but still allows self-processing
additional information
additional information
leader proteinase self-processes inefficiently at the L(pro)/VP4 cleavage site Lys-Leu-Lys-Gly-Ala-Gly when the leucine at position P2 is replaced by phenylalanine: Molecular modeling and energy minimization identifies the L(pro) residue L143 as being responsible for this discrimination
additional information
-
a mutant virus A12-LLV2 lacking the leader proteinase is attenuated in cell culture and susceptible animals due to the inability of the mutant virus to block the expression of type I interferon alpha/beta, the blockade results in the IFN-induced inhibition of FMDV replication, overview
additional information
-
mutation of the viral polyprotein self-processing cleavage site QRKLK*GAGQ, replacement by several variants of the two protein substrate elIF4G cleavage sites ANLG*RTTL and LNVG*SRRS, overview
additional information
-
Lpro regulates the activity of nuclear factor kappa B. Analysis of NF-kappa B-dependent reporter gene expression in BHK-21 cells (baby hamster kidney cells strain 21), demonstrate that infection with wild-type virus has an inhibitory effect compared to infection with a genetically engineered mutant (A12-LLV2) lacking the leader coding region
additional information
-
introduction of FLAG- and HA-tag on the small tetracysteine tc motif CCGPCC of cDNA-derived mutant FMDV A24-L1123, the mutant shows a small plaque phenotype similar to the parental A24-L1123 mutant. Expression of the Flag- or tc-tagged Lab protein is abolished or greatly diminished in these viruses. The A24-L1123/Flag virus acquires an extra base in the inter-AUG region that results in new AUG codons in-frame with the second AUG, and produced a larger Lb protein. This N-terminal extension of the Lb protein in mutant A24-L1123/Flag does not affect virus viability or L functions in cell culture
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate precipitation, Mono Q column chromatography, and Superdex 75 gel filtration
-
recombinant enzyme mutants from Escherichia coli by gel filtration
-
recombinant GST-tagged enzyme from Escherichia coli strain JM101 by glutathione affinity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of FLAG- and HA-tagged FMDV A24-L1123 mutant enzyme in LF-BK cells. T7 RNA transcripts of SpeI-digested pA24-WT, pA24-L1123 and pA24-L tag mutants, as well as transcript of control plasmid pL, are translated in vitro in rabbit reticulocyte lysates. All synthesized L mutant proteins are able to cleave themselves from the precursor L-Vp4-Vp2', the Lbeta band is absent in all L mutant translation reactions. The tn insertion in these mutant L plasmids forces translation initiation in vitro from other than the second AUG codon
-
expression of GST-tagged enzyme in Escherichia coli strain JM101
-
expression of wild-type and mutant enzymes by in vitro transcription and translation using rabbit reticulocyte lysate
-
PK-15 cells are transfected with a HA-tagged Labpro expression construct, together with a luciferase reporter plasmid with the porcine IFN-alpha1 promoter or the IFN-beta promoter and pRL-TK. At 24 h post-transfection, the cells were further transfected or mock-transfected with poly(I:C) followed by the dual-luciferase assay, quantitative real-time RT-PCR, overview
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
-
the enzym eis a target for inhibitor design for inhibition of viral replication
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kirchweger, R.; Ziegler, E.; Lamphear, B.J.; Waters, D.; Liebig, H.D.; Sommergruber, W.; Sobrino, F.; Hohenadl, C.; Blaas, D.; Rhoads, R.E.; Skern, T.
Foot-and-mouth disease virus leader proteinase: purification of the Lb form and determination of its cleavage site on eIF-4gamma
J. Virol.
68
5677-5684
1994
Foot-and-mouth disease virus
Piccone, M.E.; Zellner, M.; Kumosinski, T.F.; Mason, P.W.; Grubman, M.J.
Identification of the active-site residues of the L proteinase of foot-and-mouth disease virus
J. Virol.
69
4950-4956
1995
Foot-and-mouth disease virus
Guarne, A.; Hampoelz, B.; Glaser, W.; Carpena, X.; Torma, J.; Fita, I.; Skern, T.
Structural and biochemical features distinguish the foot-and-mouth disease virus leader proteinase from other papain-like enzymes
J. Mol. Biol.
302
1227-1240
2000
Foot-and-mouth disease virus
Glaser, W.; Skern, T.
Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro
FEBS Lett.
480
151-155
2000
Foot-and-mouth disease virus
Guarne, A.; Tormo, J.; Kirchweger, R.; Pfistermueller, D.; Fita, I.; Skern, T.
Structure of the foot-and-mouth disease virus leader protease: a papain-like fold adapted for self-processing and eIF4G recognition
EMBO J.
17
7469-7479
1998
Foot-and-mouth disease virus
Piccone, M.E.; Sira, S.; Zellner, M.; Grubman, M.J.
Expression in Escherichia coli and purification of biologically active L proteinase of foot-and-mouth disease virus
Virus Res.
35
263-275
1995
Foot-and-mouth disease virus
Skern, T.; Fita, I.; Guarne, A.
A structural model of picornavirus leader proteinases based on papain and bleomycin hydrolase
J. Gen. Virol.
79
301-307
1998
Foot-and-mouth disease virus
Ziegler, E.; Borman, A.M.; Kirchweger, R.; Skern, T.; Kean, K.M.
Foot-and-mouth disease virus Lb proteinase can stimulate rhinovirus and enterovirus IRES-driven translation and cleave several proteins of cellular and viral origin
J. Virol.
69
3465-3474
1995
Foot-and-mouth disease virus
Kuehnel, E.; Cencic, R.; Foeger, N.; Skern, T.
Foot-and-mouth disease virus leader proteinase: specificity at the P2 and P3 positions and comparison with other papain-like enzymes
Biochemistry
43
11482-11490
2004
Foot-and-mouth disease virus, Foot-and-mouth disease virus FMDV
Foeger, N.; Kuehnel, E.; Cencic, R.; Skern, T.
The binding of foot-and-mouth disease virus leader proteinase to eIF4GI involves conserved ionic interactions
FEBS J.
272
2602-2611
2005
Foot-and-mouth disease virus, Foot-and-mouth disease virus FMDV
Strong, R.; Belsham, G.J.
Sequential modification of translation initiation factor eIF4GI by two different foot-and-mouth disease virus proteases within infected baby hamster kidney cells: Identification of the 3Cpro cleavage site
J. Gen. Virol.
85
3817
2004
Foot-and-mouth disease virus
-
de Los Santos, T.; de Avila Botton, S.; Weiblen, R.; Grubman, M.J.
The leader proteinase of foot-and-mouth disease virus inhibits the induction of beta interferon mRNA and blocks the host innate immune response
J. Virol.
80
1906-1914
2006
Foot-and-mouth disease virus, Foot-and-mouth disease virus FMDV
Cencic, R.; Mayer, C.; Juliano, M.A.; Juliano, L.; Konrat, R.; Kontaxis, G.; Skern, T.
Investigating the substrate specificity and oligomerisation of the leader protease of foot and mouth disease virus using NMR
J. Mol. Biol.
373
1071-1087
2007
Foot-and-mouth disease virus
de Los Santos, T.; Diaz-San Segundo, F.; Grubman, M.J.
Degradation of nuclear factor kappa B during foot-and-mouth disease virus infection
J. Virol.
81
12803-12815
2007
Foot-and-mouth disease virus
Mayer, C.; Neubauer, D.; Nchinda, A.T.; Cencic, R.; Trompf, K.; Skern, T.
Residue L143 of the foot-and-mouth disease virus leader proteinase is a determinant of cleavage specificity
J. Virol.
82
4656-4659
2008
Foot-and-mouth disease virus (P03305)
Zunszain, P.A.; Knox, S.R.; Sweeney, T.R.; Yang, J.; Roque-Rosell, N.; Belsham, G.J.; Leatherbarrow, R.J.; Curry, S.
Insights into cleavage specificity from the crystal structure of foot-and-mouth disease virus 3C protease complexed with a peptide substrate
J. Mol. Biol.
395
375-389
2010
Foot-and-mouth disease virus
Wang, D.; Fang, L.; Luo, R.; Ye, R.; Fang, Y.; Xie, L.; Chen, H.; Xiao, S.
Foot-and-mouth disease virus leader proteinase inhibits dsRNA-induced type I interferon transcription by decreasing interferon regulatory factor 3/7 in protein levels
Biochem. Biophys. Res. Commun.
399
72-78
2010
Foot-and-mouth disease virus
Nogueira Santos, J.A.; Assis, D.M.; Gouvea, I.E.; Judice, W.A.; Izidoro, M.A.; Juliano, M.A.; Skern, T.; Juliano, L.
Foot and mouth disease leader protease (Lb(pro)): Investigation of prime side specificity allows the synthesis of a potent inhibitor
Biochimie
94
711-718
2011
Foot-and-mouth disease virus
Piccone, M.E.; Diaz-San Segundo, F.; Kramer, E.; Rodriguez, L.L.; de los Santos, T.
Introduction of tag epitopes in the inter-AUG region of foot and mouth disease virus: effect on the L protein
Virus Res.
155
91-97
2011
Foot-and-mouth disease virus
Steinberger, J.; Skern, T.
The leader proteinase of foot-and-mouth disease virus: structure-function relationships in a proteolytic virulence factor
Biol. Chem.
395
1179-1185
2014
Foot-and-mouth disease virus
Steinberger, J.; Kontaxis, G.; Rancan, C.; Skern, T.
Comparison of self-processing of foot-and-mouth disease virus leader proteinase and porcine reproductive and respiratory syndrome virus leader proteinase nsp1alpha
Virology
443
271-277
2013
Foot-and-mouth disease virus, porcine reproductive and respiratory syndrome virus
Steinberger, J.; Grishkovskaya, I.; Cencic, R.; Juliano, L.; Juliano, M.A.; Skern, T.
Foot-and-mouth disease virus leader proteinase: structural insights into the mechanism of intermolecular cleavage
Virology
468-470
397-408
2014
Foot-and-mouth disease virus (P03305)
EXTERNAL LINKS (specific for EC-Number 3.4.22.46)
Transporter Classification Database (TCDB): 1.A.85.1.4, 1.A.85.1.8
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