3.4.22.B49: cathepsin L1
This is an abbreviated version!
For detailed information about cathepsin L1, go to the full flat file.
Word Map on EC 3.4.22.B49
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3.4.22.B49
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cathepsins
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fasciola
-
hepatica
-
fluke
-
fasciolosis
-
metacercariae
-
helminth
-
gigantica
-
medicine
-
excysted
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trematode
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excretory-secretory
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immunodiagnosis
-
agriculture
-
mimotopes
-
diagnostics
- 3.4.22.B49
- cathepsins
- fasciola
- hepatica
- fluke
-
fasciolosis
-
metacercariae
-
helminth
- gigantica
- medicine
-
excysted
-
trematode
-
excretory-secretory
-
immunodiagnosis
- agriculture
-
mimotopes
- diagnostics
Reaction
clear preference for Arg at P1 position (Lys, Glu, Thr, and Met are less efficient). FheCL1 shows distinct preference for hydrophobic amino acids in the P2, Leu is favored. Cathepsin L1 can accommodate Pro in the P2 position, but less efficiently than cathepsin L2. FheCL1 produces clear degradation fragments from collagen =
Synonyms
cat-L1H, cathepsin L1, cathepsin L1 cysteine protease, cathepsin L1 protease, cathepsin L1 proteinase, cathepsin L1g, cathepsin L1H, CatL1, CgCTSL1, CGI_10027418, CL1, CPFhW, CTSL1, cysteine proteinase 3, Da-CTSL1, FgCatL1H, FhCL1, FheCL1, FhpCL1
ECTree
3.4.22.B49 cathepsin L1Advanced search results
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results (Substrates Products
Substrates Products on EC 3.4.22.B49 - cathepsin L1
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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
acetyl-FR-7-amido-4-trifluoromethyl coumarin + H2O
acetyl-FR + 7-amino-4-trifluoromethyl coumarin
-
-
-
?
benzoyl-Phe-Val-Arg-4-methylcoumarinyl-7-amide + H2O
benzoyl-Phe-Val-Arg + 7-amino-4-methylcoumarin
-
cathepsin L1
-
-
?
benzoyl-Phe-Val-Arg-7-amido-4-methylcoumarin + H2O
benzoyl-Phe-Val-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
benzyloxycarbonyl-Arg-4-methylcoumarinyl-7-amide + H2O
benzyloxycarbonyl-Arg + 7-amino-4-methylcoumarin
-
cathepsin L1
-
-
?
benzyloxycarbonyl-Arg-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
benzyloxycarbonyl-Arg-Arg-4-methylcoumarinyl-7-amide + H2O
benzyloxycarbonyl-Arg-Arg + 7-amino-4-methylcoumarin
-
cathepsin L1
-
-
?
benzyloxycarbonyl-Arg-Arg-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-Arg-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
benzyloxycarbonyl-L-Leu-L-Arg-4-methylcoumarinyl-7-amide + H2O
benzyloxycarbonyl-L-Leu-L-Arg + 7-amino-4-methylcoumarin
FheCL1
-
-
?
benzyloxycarbonyl-L-Phe-L-Arg-4-methylcoumarinyl-7-amide + H2O
benzyloxycarbonyl-L-Phe-L-Arg + 7-amino-4-methylcoumarin
benzyloxycarbonyl-L-phenylalanyl-L-arginine 4-methylcoumarinyl-7-amide + H2O
?
-
-
-
-
?
benzyloxycarbonyl-L-Pro-L-Arg-4-methylcoumarinyl-7-amide + H2O
benzyloxycarbonyl-L-Pro-L-Arg + 7-amino-4-methylcoumarin
FheCL1
-
-
?
benzyloxycarbonyl-Leu-Arg-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-Leu-Arg + 7-amino-4-methylcoumarin
-
-
-
?
benzyloxycarbonyl-Phe-Arg-4-methylcoumarinyl-7-amide + H2O
benzyloxycarbonyl-Phe-Arg + 7-amino-4-methylcoumarin
-
cleaved by cathepsin L2 with much greater affinity than by cathepsin L1
-
-
?
benzyloxycarbonyl-Phe-Arg-4-nitroanilide + H2O
benzyloxycarbonyl-Phe-Arg + 4-nitroaniline
-
-
-
-
?
benzyloxycarbonyl-Phe-Arg-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-Phe-Arg + 7-amino-4-methylcoumarin
benzyloxycarbonyl-Phe-Arg-7-amido-4-trifluoromethylcoumarin + H2O
benzyloxycarbonyl-Phe-Arg + 7-amino-4-trifluoromethylcoumarin
-
best substrate
-
-
?
benzyloxycarbonyl-Phe-Phe-Arg-7-amido-4-methylcoumarin + H2O
?
-
renatured CPFhW
-
-
?
benzyloxycarbonyl-Pro-Arg-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-Pro-Arg + 7-amino-4-methylcoumarin
-
-
-
?
Collagen + H2O
?
whereas FheCL1 produces clear degradation fragments, FheCL2 degrades the collagen completely, particularly at pH 4.0, indicating that only the latter cleaves efficiently within the helical structures
-
-
?
Fibrinogen + H2O
?
enzyme FhCL3 is capable of degradation of the fibrinogen alpha-chain, beta-chain, and gamma-chain
-
-
?
H-Leu-Val-Tyr-4-methylcoumarinyl-7-amide + H2O
H-Leu-Val-Tyr + 7-amino-4-methylcoumarin
-
cleaved by cathepsin L2 with much greater affinity than by cathepsin L1
-
-
?
H-Leu-Val-Tyr-7-amido-4-methylcoumarin + H2O
H-Leu-Val-Tyr + 7-amino-4-methylcoumarin
-
-
-
-
?
human IgG + H2O
?
-
both cathepsins L produce similar degradation patterns and cleave all human IgG subclasses at the hinge region, yielding at pH 7.3 and 37°C Fab and Fc fragments in the case of IgG1 and IgG3 or Fab(2) and Fc in IgG2 and IgG4. Both liver fluke cathepsins L cleave the peptide bonds 237His-Thr, 237Glu-Cys, 233Gly-Asp, and 241Ser-Cys of the gamma1, gamma2, gamma3, and gamma4 H chains, respectively. Therefore, the enzymes are interacting with the following P3-P'3 sequences, Lys-Thr-His-Thr-Cys-Pro, Cys-Val-Glu-Asp-Pro-Pro, Pro-Leu-Gly-Asp-Thr-Thr, and Cys-Pro-Ser-Cys-Pro-Ala. The specificity of the liver fluke cathepsins L for peptide bonds in proteins is less defined. The P1 position, for instance, can be occupied by hydrophobic, hydrophilic, acidic, or basic residues. The P3 and P2 positions are occupied by hydrophobic amino acids with the exception of the gamma1 sequence which contains a basic lysine and a hydrophilic threonine, respectively. In addition the specificity between the enzyme and its substrate would depend on which of the amino acids of the substrate can be really exposed to the active site
-
-
?
Leu-Val-Tyr-7-amido-4-methylcoumarin + H2O
Leu-Val-Tyr + 7-amino-4-methylcoumarin
-
cleaved by cathepsin L2 with much greater affinity than by cathepsin L1
-
-
?
N-benzyloxycarbonyl-FR-4-nitroanilide + H2O
N-benzyloxycarbonyl-FR + 4-nitroaniline
-
-
-
?
N-benzyloxycarbonyl-FR-7-amido-4-trifluoromethylcoumarin + H2O
N-benzyloxycarbonyl-FR + 7-amino-4-trifluoromethylcoumarin
best substrate
-
-
?
N-benzyloxycarbonyl-GPR-7-amido-4-methylcoumarin + H2O
N-benzyloxycarbonyl-GPR + 7-amino-4-methylcoumarin
-
-
-
?
N-benzyloxycarbonyl-VVR-7-amido-4-methylcoumarin + H2O
N-benzyloxycarbonyl-VVR + 7-amino-4-methylcoumarin
-
-
-
?
procathepsin L1 + H2O
?
-
procathepsin L1 autocatalytically processes and activates to its mature enzyme (FheCL1) over a wide pH range 4.0-7.3. Activation is more rapid at low pH. Maturation initiates with cleavages of a small proportion of molecules within the central region of the prosegment, possibly by intramolecular events. Activation to fully mature enzymes is achieved by a precise intermolecular cleavage at a Leu12-Ser11-/-His10 sequence within the nonconserved C-terminal region of the prosegment. Active site variant FheproCL1C26G and a double variant FheproCL1L12P/C26G cannot autocatalytically process. The former is susceptible to trans-processing at a Leu12-Ser11-/-His10 sequence by preactivated FheCL1, but the latter is not
-
-
?
succinyl-Ala-Phe-Lys-4-methylcoumarinyl-7-amide + H2O
succinyl-Ala-Phe-Lys + 7-amino-4-methylcoumarin
-
cathepsin L1
-
-
?
succinyl-Ala-Phe-Lys-7-amido-4-methylcoumarin + H2O
tosyl-Ala-Phe-Lys + 7-amino-4-methylcoumarin
-
-
-
-
?
succinyl-Leu-Leu-Val-Tyr-4-methylcoumarinyl-7-amide + H2O
succinyl-Leu-Leu-Val-Tyr + 7-amino-4-methylcoumarin
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cathepsin L1
-
-
?
succinyl-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin + H2O
succinyl-Leu-Leu-Val-Tyr + 7-amino-4-methylcoumarin
-
-
-
-
?
t-butyloxycarbonyl-Val-Leu-Lys-7-amido-4-methylcoumarin + H2O
t-butyloxycarbonyl-Val-Leu-Lys + 7-amino-4-methylcoumarin
-
-
-
-
?
t-butyloxycarbonyl-Val-Pro-Arg-7-amido-4-methylcoumarin + H2O
t-butyloxycarbonyl-Val-Pro-Arg + 7-amino-4-methylcoumarin
-
cleaved by cathepsin L2 with much greater affinity than by cathepsin L1
-
-
?
tert-butoxycarbonyl-Gly-Pro-Arg-4-methylcoumarinyl-7-amide + H2O
tert-butoxycarbonyl-Gly-Pro-Arg + 7-amino-4-methylcoumarin
FheCL1
-
-
?
tert-butyloxycarbonyl-Val-Leu-Lys-4-methylcoumarinyl-7-amide + H2O
tert-butyloxycarbonyl-Val-Leu-Lys + 7-amino-4-methylcoumarin
-
cathepsin L1
-
-
?
tert-butyloxycarbonyl-Val-Pro-Arg-4-methylcoumarinyl-7-amide + H2O
tert-butyloxycarbonyl-Val-Pro-Arg + 7-amino-4-methylcoumarin
-
cleaved by cathepsin L2 with much greater affinity than by cathepsin L1
-
-
?
tosyl-Ala-Phe-Lys-4-methylcoumarinyl-7-amide + H2O
tosyl-Ala-Phe-Lys + 7-amino-4-methylcoumarin
-
cathepsin L1
-
-
?
tosyl-Gly-Pro-Arg-4-methylcoumarinyl-7-amide + H2O
tosyl-Gly-Pro-Arg + 7-amino-4-methylcoumarin
tosyl-Gly-Pro-Arg-7-amido-4-methylcoumarin + H2O
tosyl-Gly-Pro-Arg + 7-amino-4-methylcoumarin
-
cleaved by cathepsin L2 with much greater affinity than by cathepsin L1
-
-
?
tosyl-Gly-Pro-Lys-4-methylcoumarinyl-7-amide + H2O
tosyl-Gly-Pro-Lys + 7-amino-4-methylcoumarin
-
cleaved by cathepsin L2 with much greater affinity than by cathepsin L1
-
-
?
tosyl-Gly-Pro-Lys-7-amido-4-methylcoumarin + H2O
tosyl-Gly-Pro-Lys + 7-amino-4-methylcoumarin
-
cleaved by cathepsin L2 with much greater affinity than by cathepsin L1
-
-
?
Z-Phe-Arg-OMe + SerNH2
Z-Phe-Arg-Ser-NH2 + methanol
-
peptide synthesis
-
-
?
benzyloxycarbonyl-L-Phe-L-Arg-4-methylcoumarinyl-7-amide + H2O
benzyloxycarbonyl-L-Phe-L-Arg + 7-amino-4-methylcoumarin
-
FheCL1
-
-
?
benzyloxycarbonyl-L-Phe-L-Arg-4-methylcoumarinyl-7-amide + H2O
benzyloxycarbonyl-L-Phe-L-Arg + 7-amino-4-methylcoumarin
FheCL1
-
-
?
benzyloxycarbonyl-Phe-Arg-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-Phe-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
benzyloxycarbonyl-Phe-Arg-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-Phe-Arg + 7-amino-4-methylcoumarin
-
-
-
?
benzyloxycarbonyl-Phe-Arg-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-Phe-Arg + 7-amino-4-methylcoumarin
-
cleaved by cathepsin L2 with much greater affinity than by cathepsin L1
-
-
?
Hemoglobin + H2O
?
-
Fasciola hepatica secretes cathepsin L cysteine proteases to invade its host, migrate through tissues and digest hemoglobin, its main source of amino acids. FheCL1 can degrade hemoglobin to small peptides, predominantly of 414 residues, but cannot release free amino acids. It is suggested that hemoglobin degradation is not completed in the gut lumen but the resulting peptides are absorbed by the gut epithelial cells for further processing by intracellular di- and amino-peptidases to free amino acids that are distributed through the parasite tissue for protein anabolism. The action of FheCL1 is enhanced by glutathione, the major reducing agent found in red blood cells
-
-
?
Hemoglobin + H2O
?
FhCL1 cleaves substrates with hydrophobic residues (Phe and Leu) in the P2 position with catalytic rates (kcat/Km) that are 25- and eightfold greater, respectively, than FhCL2. In comparison to human cathepsin L, which can accommodate a wide range of amino acids in the S2 subsite, the S2 subsite of FhCL1 is restricted. Hydrophobic residues are most susceptible to cleavage, in the order Leu > Val > Ala > Phe. Together, these four residues make up about 42% of the hemoglobin molecule and, therefore, it seems that FhCL1 has been specifically adapted to degrade the host substrate, which it exploits as nutrient. Substrates with proline in the P2 position, which are good substrates for FhCL2 are poorly cleaved by FhCL1 (and not at all by human cathepsin L)
-
-
?
Hemoglobin + H2O
?
-
FheCL1 can degrade hemoglobin to small peptides, predominantly of 414 residues, but cannot release free amino acids. FheCL1 can not cleave its natural substrate hemoglobin in the pH range pH 5.5 and pH 7.0. Digestion occurs only at or below pH 4.5, which coincides with pH-induced dissociation of the hemoglobin tetramer. The acidic pH of the parasite relaxes the hemoglobin structure, making it susceptible to proteolysis by FheCL1. The P1 position could be occupied by many amino acids but most preferentially Leu. FheCL1 preferentially cleaves bonds where the P2 position is occupied with hydrophobic residues (in order of decreasing efficiency: Leu, Val, Ala, Phe) and is observed for the digestion of both hemoglobin-alpha and hemoglobin-beta
-
-
?
Hemoglobin + H2O
?
-
enzyme does not cleave its natural substrate hemoglobin in the pH range pH 5.5 and pH 7.0. Digestion occurs only at pH 4.5, which coincides with pH-induced dissociation of the hemoglobin tetramer
degradation to small peptides of 4-14 residues, no release of free amino acids
-
?
Hemoglobin + H2O
?
purified recombinant CL1 is not able to hydrolyze hemoglobin
-
-
?
ovalbumin + H2O
?
-
FheCL1 can degrade ovalbumin from pH 3.5 to pH 8.0
-
-
?
tosyl-Gly-Pro-Arg-4-methylcoumarinyl-7-amide + H2O
tosyl-Gly-Pro-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
tosyl-Gly-Pro-Arg-4-methylcoumarinyl-7-amide + H2O
tosyl-Gly-Pro-Arg + 7-amino-4-methylcoumarin
-
cleaved by cathepsin L2 with much greater affinity than by cathepsin L1
-
-
?
tosyl-Gly-Pro-Arg-4-methylcoumarinyl-7-amide + H2O
tosyl-Gly-Pro-Arg + 7-amino-4-methylcoumarin
FheCL1
-
-
?
additional information
?
-
-
benzyloxycarbonyl-Gly-Pro-Atg-7-amido-4-methylcoumarin and benzyloxycarbonyl-Val-Val-Arg-7-amido-4-methylcoumarin are not hydrolyzed
-
-
?
additional information
?
-
-
does not hydrolyze Arg-4-nitroanilide, N-succinyl-Ala-Ala-Pro-Phe-4-nitroanilide, benzyloxycarbonyl-Gly-Pro-Arg-7-amido-4-methylcoumarin, and benzyloxycarbonyl-Val-Val-Arg-7-amido-4-methylcoumarin
-
-
?
additional information
?
-
substrate specificity supports the hypothesis that Diaprepes abbreviatus CTSL1 is a unique basic cathepsin L and protease inhibitor studies also suggest unique activity, unlike other characterized acidic cathepsin Ls. No activity with N-succinyl-AAPF-4-nitroanilide and HR-4-nitroanilide
-
-
?
additional information
?
-
-
substrate specificity supports the hypothesis that Diaprepes abbreviatus CTSL1 is a unique basic cathepsin L and protease inhibitor studies also suggest unique activity, unlike other characterized acidic cathepsin Ls. No activity with N-succinyl-AAPF-4-nitroanilide and HR-4-nitroanilide
-
-
?
additional information
?
-
-
the enzyme mediates kinin release from high molecular weight kininigen
-
-
?
additional information
?
-
-
the enzyme facilitates the penetration of the parasite though the tissue of its host, and also participates in functions such as feeding and immune evasion
-
-
?
additional information
?
-
-
cathepsin L1 and cathepsin L2 proteinases may be the prime mechanism by which the parasite penetrates tissue
-
-
?
additional information
?
-
-
renatured enzyme shows no activity with benzyloxycarbonyl-Phe-Arg-beta-naphthylamide
-
-
?
additional information
?
-
wild-type FheCL1 shows clear preference for Arg at P1. Other residues accommodated in this position including Lys, Glu, Thr, and Met are all cleaved at similar relative rates to that observed for human cathepsin L and cathepsin K. Similar results are obtained for the variants FheCL1 L67Y and FheCL1 L205A. FheCL1 shows distinct preference for hydrophobic amino acids in the P2, Leu is favored. FheCL1 and FheCL2 are similar to cathepsin K with regard to their preference for a P2 Leu over Phe (human cathepsin L has a preference for P2 Phe over Leu). Both enzymes can accommodate Pro in the P2 position, but this is more readily accepted by FheCL2 compared with FheCL1. Neither enzyme, however, cleaves substrates with this residue in the P2 position as readily as human cathepsin K
-
-
?
additional information
?
-
-
wild-type FheCL1 shows clear preference for Arg at P1. Other residues accommodated in this position including Lys, Glu, Thr, and Met are all cleaved at similar relative rates to that observed for human cathepsin L and cathepsin K. Similar results are obtained for the variants FheCL1 L67Y and FheCL1 L205A. FheCL1 shows distinct preference for hydrophobic amino acids in the P2, Leu is favored. FheCL1 and FheCL2 are similar to cathepsin K with regard to their preference for a P2 Leu over Phe (human cathepsin L has a preference for P2 Phe over Leu). Both enzymes can accommodate Pro in the P2 position, but this is more readily accepted by FheCL2 compared with FheCL1. Neither enzyme, however, cleaves substrates with this residue in the P2 position as readily as human cathepsin K
-
-
?
additional information
?
-
-
enzyme preferentially cleaves bonds where the P2 position is occupied with hydrophobic residues, this preference follows the order Leu>Val>Ala>Phe, and is observed for the digestion of both hemoglobin-alpha and hemoglobin-beta
-
-
?
