3.4.22.46: L-peptidase

This is an abbreviated version!
For detailed information about L-peptidase, go to the full flat file.

Reaction

autocatalytically cleaves itself from the polyprotein of the foot-and-mouth disease virus by hydrolysis of a Lys-/-Gly bond, but then cleaves host cell initiation factor eIF-4G at bonds -Gly-/-Arg- and -Lys-/-Arg- =

Synonyms

3C protease, 3Cpro, Eukaryotic signal peptidase, Eukaryotic signal proteinase, FMDV 3Cpro, foot-and-mouth disease virus 3C protease, L protein, L proteinase, Lab protein, Lb proC, Lbpro, Leader peptidase, leader peptidase B, leader peptidase NisP, Leader peptide hydrolase, leader protease, Leader proteinase, leaderprotease L1, leaderprotease L2, LepB, Lpro, nisin leader peptidase, NisP, nsp1alpha, P1a protein, Peptidase, signal, Prokaryotic leader peptidase, Prokaryotic signal peptidase, Prokaryotic signal proteinase, Propeptidase, Proteinase, eukaryotic signal, Proteinase, signal, Signal peptidase, Signalase, sLbpro

ECTree

     3 Hydrolases

         3.4 Acting on peptide bonds (peptidases)

             3.4.22 Cysteine endopeptidases

                3.4.22.46 L-peptidase

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Results	in table
15	AA Sequence
1	Application
1	CAS Registry Number
18	Cloned(Commentary)
4	Crystallization (Commentary)
11	General Information
11	Inhibitors
6	Ki Value [mM]
1	KM Value [mM]
2	Localization
11	Molecular Weight [Da]
35	Natural Substrates/ Products (Substrates)
40	Organism
26	PDB ID
4	pH Optimum
1	pH Range
2	Posttranslational Modification
26	Protein Variants
8	Purification (Commentary)
1	Reaction
1	Reaction Type
33	Reference
1	Source Tissue
1	Specific Activity [micromol/min/mg]
1	Storage Stability
62	Substrates and Products (Substrate)
9	Subunits
67	Synonyms
3	Temperature Optimum [°C]

Substrates Products

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Substrates Products on EC 3.4.22.46 - L-peptidase

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SUBSTRATE

PRODUCT                       

REACTION DIAGRAM

ORGANISM

UNIPROT

COMMENTARY
(Substrate)

LITERATURE
(Substrate)

COMMENTARY
(Product)

LITERATURE
(Product)

Reversibility
r=reversible
ir=irreversible
?=not specified

Abz-KLKGAGQ-EDDnp + H2O

Abz-KLK + GAGQ-EDDnp

Foot-and-mouth disease virus

-

hydrolysis of FRET peptides

717297

-

-

?

Edans-EGAVSVRSQEIK-Dabcyl + H2O

?

Lactococcus lactis

D9IXC0

-

731065

-

-

?

eukaryotic initiation factor 4G + H2O

?

Foot-and-mouth disease virus

-

Lbpro cleaves two homologues of the host cell protein. Lbpro possesses specific binding sites at the non-prime side from S1 down to S7

717297

-

-

?

eukaryotic initiation factor eIF4G + H2O

?

3 entries

eukaryotic initiation factor eIF4GI + H2O

?

6 entries

eukaryotic initiation factor eIF4GII + H2O

?

6 entries

eukaryotic translation initiation factor eIF4GI + H2O

?

6 entries

foot-and-mouth disease leader protein + H2O

?

3 entries

human cyclin A + H2O

?

Foot-and-mouth disease virus

-

-

137305

-

-

?

mengovirus polypeptide + H2O

?

Foot-and-mouth disease virus

-

-

137305

-

-

?

nisin + H2O

?

Lactococcus lactis

D9IXC0

the final step in nisin maturation is the proteolytic cleavage of the first 23 amino-terminal residues by NisP

731065

-

-

?

nisin-(leader peptide) + H2O

nisin + leader peptide

2 entries

nuclear factor-kappaB + H2O

?

Foot-and-mouth disease virus

-

-

731405

-

-

?

poliovirus replicase-related polypeptide + H2O

?

Foot-and-mouth disease virus

-

-

137305

-

-

?

RNA helicase LGP2 + H2O

?

2 entries

SFANLGRTTL + H2O

SFANLG + RTTL

Foot-and-mouth disease virus

P03305

poor substrate for both isoforms Lbpro and sLbpro

732975

-

-

?

Val-Gln-Arg-Lys-Leu-Lys-4-methylcoumarin 7-amide + H2O

Val-Gln-Arg-Lys-Leu-Lys + 7-amino-4-methylcoumarin

Foot-and-mouth disease virus

-

the substrate corresponds to the six C-terminal amino acids of the leader protein

137299

-

137299

?

VQRKLGAAGQ + H2O

VQRKLG + AAGQ

Foot-and-mouth disease virus

P03305

isoform sLbpro cleaves this substrate better than isoform Lbpro

732975

-

-

?

VQRKLGRAGQ + H2O

VQRKLG + RAGQ

Foot-and-mouth disease virus

P03305

isoform sLbpro cleaves this substrate better than isoform Lbpro

732975

-

-

?

VQRKLKGAGQ + H2O

VQRKLK + GAGQ

Foot-and-mouth disease virus

P03305

isoform sLbpro cleaves this substrate better than isoform Lbpro

732975

-

-

?

VQRKLKRAGQ + H2O

VQRKLK + RAGQ

Foot-and-mouth disease virus

P03305

isoform sLbpro cleaves this substrate better than isoform Lbpro

732975

-

-

?

additional information

?

-

19 entries

eukaryotic initiation factor eIF4G + H2O

?

Foot-and-mouth disease virus

-

-

731405, 732973

-

-

?

eukaryotic initiation factor eIF4G + H2O

?

Foot-and-mouth disease virus

P03305

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

732975

-

-

?

eukaryotic initiation factor eIF4G + H2O

?

porcine reproductive and respiratory syndrome virus

-

-

732973

-

-

?

eukaryotic initiation factor eIF4GI + H2O

?

Foot-and-mouth disease virus

-

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

668547

-

-

?

eukaryotic initiation factor eIF4GI + H2O

?

Foot-and-mouth disease virus

-

eukaryotic host cell protein substrate, recognition/cleavage site is ANLG*RTTL

667582

-

-

?

eukaryotic initiation factor eIF4GI + H2O

?

Foot-and-mouth disease virus

-

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

668547

-

-

?

eukaryotic initiation factor eIF4GI + H2O

?

Foot-and-mouth disease virus FMDV

-

eukaryotic host cell protein substrate, recognition/cleavage site is ANLG*RTTL

667582

-

-

?

eukaryotic initiation factor eIF4GI + H2O

?

Foot-and-mouth disease virus FMDV

-

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

668547

-

-

?

eukaryotic initiation factor eIF4GI + H2O

?

Foot-and-mouth disease virus FMDV

-

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

668547

-

-

?

eukaryotic initiation factor eIF4GII + H2O

?

Foot-and-mouth disease virus

-

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

668547

-

-

?

eukaryotic initiation factor eIF4GII + H2O

?

Foot-and-mouth disease virus

-

eukaryotic host cell protein substrate, recognition/cleavage site is LNVG*SRRS, but not ADFG*RQTP

667582

-

-

?

eukaryotic initiation factor eIF4GII + H2O

?

Foot-and-mouth disease virus

-

eukaryotic host cell protein substrate

668547

-

-

?

eukaryotic initiation factor eIF4GII + H2O

?

Foot-and-mouth disease virus FMDV

-

eukaryotic host cell protein substrate, recognition/cleavage site is LNVG*SRRS, but not ADFG*RQTP

667582

-

-

?

eukaryotic initiation factor eIF4GII + H2O

?

Foot-and-mouth disease virus FMDV

-

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

668547

-

-

?

eukaryotic initiation factor eIF4GII + H2O

?

Foot-and-mouth disease virus FMDV

-

eukaryotic host cell protein substrate

668547

-

-

?

eukaryotic translation initiation factor eIF4GI + H2O

?

Foot-and-mouth disease virus

-

eukaryotic host cell protein substrate, cleavage causes the rapid inhibition of cellular cap-dependent protein synthesis

670093

-

-

?

eukaryotic translation initiation factor eIF4GI + H2O

?

Foot-and-mouth disease virus

-

eukaryotic host cell protein substrate, cleavage causes the rapid inhibition of cellular cap-dependent protien synthesis

669685

-

-

?

eukaryotic translation initiation factor eIF4GI + H2O

?

Foot-and-mouth disease virus

-

eukaryotic host cell protein substrate

670093

-

-

?

eukaryotic translation initiation factor eIF4GI + H2O

?

Foot-and-mouth disease virus

-

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

669685

-

-

?

eukaryotic translation initiation factor eIF4GI + H2O

?

Foot-and-mouth disease virus FMDV

-

eukaryotic host cell protein substrate, cleavage causes the rapid inhibition of cellular cap-dependent protein synthesis

670093

-

-

?

eukaryotic translation initiation factor eIF4GI + H2O

?

Foot-and-mouth disease virus FMDV

-

eukaryotic host cell protein substrate

670093

-

-

?

foot-and-mouth disease leader protein + H2O

?

Foot-and-mouth disease virus

-

-

137303

-

-

?

foot-and-mouth disease leader protein + H2O

?

Foot-and-mouth disease virus

-

cis and trans cleavage activity at the L/P1 junction

137298

-

-

?

foot-and-mouth disease leader protein + H2O

?

Foot-and-mouth disease virus

-

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

29824, 137299

-

-

?

nisin-(leader peptide) + H2O

nisin + leader peptide

Lactococcus lactis subsp. lactis

Q07596

-

752774

-

-

?

nisin-(leader peptide) + H2O

nisin + leader peptide

Lactococcus lactis subsp. lactis

Q07596

after translocation into the extracellular space, the leader peptide is cleaved by the leader peptidase NisP, resulting in active nisin. NisP recognizes the cleavage site GASPR-/-IT located at the C-terminal end of the leader peptide

752774

-

-

?

RNA helicase LGP2 + H2O

?

Foot-and-mouth disease virus

-

-

755214

-

-

?

RNA helicase LGP2 + H2O

?

Foot-and-mouth disease virus

-

LGP2 cleavage by the Leader protease of aphthoviruses may represent an antagonistic mechanism for immune evasion

755214

-

-

?

additional information

?

-

Foot-and-mouth disease virus

-

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

137299

-

-

?

additional information

?

-

Foot-and-mouth disease virus

-

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

670093

-

-

?

additional information

?

-

Foot-and-mouth disease virus

-

elIF4GI cleavage site mapping

669685

-

-

?

additional information

?

-

Foot-and-mouth disease virus

-

substrate recognition and cleavage site specificity, overview

668547

-

-

?

additional information

?

-

Foot-and-mouth disease virus

-

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

667582

-

-

?

additional information

?

-

Foot-and-mouth disease virus

-

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

717297

-

-

?

additional information

?

-

Foot-and-mouth disease virus

-

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

709535

-

-

?

additional information

?

-

Foot-and-mouth disease virus

-

the enzyme cleaves itself off the nascent viral polyprotein

732973

-

-

?

additional information

?

-

Foot-and-mouth disease virus FMDV

-

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

667582

-

-

?

additional information

?

-

Foot-and-mouth disease virus FMDV

-

substrate recognition and cleavage site specificity, overview

668547

-

-

?

additional information

?

-

Foot-and-mouth disease virus FMDV

-

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

670093

-

-

?

additional information

?

-

Lactococcus lactis

D9IXC0

the enzyme possesses an auto-cleavage site between residues Arg647 and Ser648

731065

-

-

?

additional information

?

-

Lactococcus lactis

-

the enzyme possesses an auto-cleavage site between residues Arg647 and Ser648

731065

-

-

?

translation initiation factor eIF4G + H2O

additional information

-

Foot-and-mouth disease virus

-

-

137299

-

-

?

translation initiation factor eIF4G + H2O

additional information

-

Foot-and-mouth disease virus

-

-

137301

-

-

?

translation initiation factor eIF4G + H2O

additional information

-

Foot-and-mouth disease virus

-

-

137303

-

-

?

translation initiation factor eIF4G + H2O

additional information

-

Foot-and-mouth disease virus

-

-

29824

characterization of cleavage products, primary cleavage of rabbit reticulocyte eIF-4-gamma occurs between Gly479-Arg480, complete proteolysis after 12 h

29824

?

translation initiation factor eIF4G + H2O

additional information

-

Foot-and-mouth disease virus

-

very rapid reaction

137300

-

-

?

translation initiation factor eIF4G + H2O

additional information

-

Foot-and-mouth disease virus

-

i.e. p220

137298

-

-

?