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Literature summary for 3.4.22.1 extracted from

  • Beckham, S.A.; Piedrafita, D.; Phillips, C.I.; Samarawickrema, N.; Law, R.H.; Smooker, P.M.; Quinsey, N.S.; Irving, J.A.; Greenwood, D.; Verhelst, S.H.; Bogyo, M.; Turk, B.; Coetzer, T.H.; Wijeyewickrema, L.C.; Spithill, T.W.; Pike, R.N.
    A major cathepsin B protease from the liver fluke Fasciola hepatica has atypical active site features and a potential role in the digestive tract of newly excysted juvenile parasites (2009), Int. J. Biochem. Cell Biol., 41, 1601-1612.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
drug development the enzyme is a target for therapeutic inhibitors or vaccination Fasciola hepatica

Cloned(Commentary)

Cloned (Comment) Organism
expression of His-tagged pro-catB1 in Pichia pastoris Fasciola hepatica
expression of mutant enzymes in Pichia pastoris Homo sapiens

Protein Variants

Protein Variants Comment Organism
H110A/S115A site-directed mutagenesis, the S115A mutation eliminates an O-glycosylation site Homo sapiens
S115A site-directed mutagenesis, the S115A mutation eliminates an O-glycosylation site Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
CA-074Me
-
Fasciola hepatica
CA-074Me
-
Homo sapiens
E-64 an irreversible cysteine protease inhibitor Fasciola hepatica
E-64 an irreversible cysteine protease inhibitor Homo sapiens
human cystatin A
-
Fasciola hepatica
human cystatin A
-
Homo sapiens
human cystatin B
-
Fasciola hepatica
Human cystatin C
-
Fasciola hepatica
Human cystatin C
-
Homo sapiens
additional information no inhibition by human cystatin B Homo sapiens
sheep cystatin B
-
Fasciola hepatica
sheep cystatin B
-
Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.007
-
N-benzyloxycarbonyl-Val-Ile-Arg-4-methylcoumarin 7-amide pH 6.0, 22°C Fasciola hepatica
0.047
-
N-benzyloxycarbonyl-Phe-Arg-4-methyl-7-amidocoumarin pH 6.0, 22°C Homo sapiens
0.06
-
Tos-Gly-Pro-Arg-4-methylcoumarin 7-amide pH 6.0, 22°C Fasciola hepatica
0.1
-
N-benzyloxycarbonyl-Arg-Arg-4-methyl-7-amidocoumarin pH 6.0, 22°C Homo sapiens
0.19
-
N-benzyloxycarbonyl-Phe-Arg-4-methylcoumarin 7-amide pH 6.0, 22°C Fasciola hepatica
0.35
-
Boc-Asp-Pro-Arg-4-methylcoumarin 7-amide pH 6.0, 22°C Fasciola hepatica
0.53
-
Boc-Val-Pro-Arg-4-methylcoumarin 7-amide pH 6.0, 22°C Fasciola hepatica
0.88
-
Tos-Gly-Pro-Arg-4-methyl-7-amidocoumarin pH 6.0, 22°C Homo sapiens
1.16
-
Boc-Asp-Pro-Arg-4-methyl-7-amidocoumarin pH 6.0, 22°C Homo sapiens
1.22
-
N-benzyloxycarbonyl-Arg-Arg-4-methylcoumarin 7-amide pH 6.0, 22°C Fasciola hepatica
1.67
-
Boc-Val-Leu-Lys-4-methyl-7-amidocoumarin pH 6.0, 22°C Homo sapiens
4.53
-
D-Val-Leu-Arg-4-methylcoumarin 7-amide pH 6.0, 22°C Fasciola hepatica

Localization

Localization Comment Organism GeneOntology No. Textmining
extracellular
-
Fasciola hepatica
-
-

Organism

Organism UniProt Comment Textmining
Fasciola hepatica
-
metacercariae are propagated and harvested from the snail species Lymnaea tormentosa
-
Homo sapiens
-
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
glycoprotein the recombinant catB1 is mixed glycosylated Fasciola hepatica
proteolytic modification the recombinant pro-catB1 is autoprocessed Fasciola hepatica

Purification (Commentary)

Purification (Comment) Organism
recombinant His-tagged pro-catB1 from Pichia pastoris by nickel affinity chromatography Fasciola hepatica
recombinant mutant enzymes from Pichia pastoris Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
gut
-
Fasciola hepatica
-
additional information liver fluke at excysted juvenile stage Fasciola hepatica
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
Boc-Asp-Pro-Arg-4-methyl-7-amidocoumarin + H2O
-
Homo sapiens Boc-Asp-Pro-Arg + 4-methyl-7-aminocoumarin
-
?
Boc-Asp-Pro-Arg-4-methylcoumarin 7-amide + H2O
-
Fasciola hepatica Boc-Asp-Pro-Arg + 7-amino-4-methylcoumarin
-
?
Boc-Val-Leu-Lys-4-methyl-7-amidocoumarin + H2O
-
Homo sapiens Boc-Val-Leu-Lys + 4-methyl-7-aminocoumarin
-
?
Boc-Val-Pro-Arg-4-methylcoumarin 7-amide + H2O
-
Fasciola hepatica Boc-Val-Pro-Arg + 7-amino-4-methylcoumarin
-
?
D-Val-Leu-Arg-4-methylcoumarin 7-amide + H2O
-
Fasciola hepatica D-Val-Leu-Arg + 7-amino-4-methylcoumarin
-
?
additional information Boc-Val-Leu-Lys-4-methylcoumarin 7-amide is no substrate of catB1. CatB1 substrate specificity, homology modelling and molecular dynamics simulations of FhcatB1 interaction with peptide substrates, molecular modelling, overview. A P2 Ile residue positions the substrate optimally for interaction with catalytic residues of the enzyme, and the enzyme lacks an occluding loop His residue crucial for exopeptidase activity. The enzyme performs autolytic processing Fasciola hepatica ?
-
?
additional information No activity with Boc-Val-Pro-Arg-4-methyl-7-amidocoumarin, Boc-Val-Leu-Lys-4-methyl-7-amidocoumarin, and D-Val-Leu-Arg-4-methyl-7-amidocoumarin. Wild-type cathepsin B exhibits exopeptidase activity Homo sapiens ?
-
?
N-benzyloxycarbonyl-Arg-Arg-4-methyl-7-amidocoumarin + H2O
-
Homo sapiens N-benzyloxycarbonyl-Arg-Arg + 4-methyl-7-aminocoumarin
-
?
N-benzyloxycarbonyl-Arg-Arg-4-methylcoumarin 7-amide + H2O
-
Fasciola hepatica N-benzyloxycarbonyl-Arg-Arg + 7-amino-4-methylcoumarin
-
?
N-benzyloxycarbonyl-Phe-Arg-4-methyl-7-amidocoumarin + H2O
-
Homo sapiens N-benzyloxycarbonyl-Phe-Arg + 4-methyl-7-aminocoumarin
-
?
N-benzyloxycarbonyl-Phe-Arg-4-methylcoumarin 7-amide + H2O
-
Fasciola hepatica N-benzyloxycarbonyl-Phe-Arg + 7-amino-4-methylcoumarin
-
?
N-benzyloxycarbonyl-Val-Ile-Arg-4-methyl-7-amidocoumarin + H2O
-
Homo sapiens N-benzyloxycarbonyl-Val-Ile-Arg + 4-methyl-7-aminocoumarin
-
?
N-benzyloxycarbonyl-Val-Ile-Arg-4-methylcoumarin 7-amide + H2O
-
Fasciola hepatica N-benzyloxycarbonyl-Val-Ile-Arg + 7-amino-4-methylcoumarin
-
?
Tos-Gly-Pro-Arg-4-methyl-7-amidocoumarin + H2O
-
Homo sapiens Tos-Gly-Pro-Arg + 4-methyl-7-aminocoumarin
-
?
Tos-Gly-Pro-Arg-4-methylcoumarin 7-amide + H2O
-
Fasciola hepatica Tos-Gly-Pro-Arg + 7-amino-4-methylcoumarin
-
?

Synonyms

Synonyms Comment Organism
CatB1
-
Fasciola hepatica

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
22
-
assay at room temperature Fasciola hepatica
22
-
hydrolytic assay and autoprocessing assay at room temperature Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.13
-
Tos-Gly-Pro-Arg-4-methylcoumarin 7-amide pH 6.0, 22°C Fasciola hepatica
0.13
-
N-benzyloxycarbonyl-Arg-Arg-4-methylcoumarin 7-amide pH 6.0, 22°C Fasciola hepatica
0.14
-
D-Val-Leu-Arg-4-methylcoumarin 7-amide pH 6.0, 22°C Fasciola hepatica
0.19
-
N-benzyloxycarbonyl-Phe-Arg-4-methylcoumarin 7-amide pH 6.0, 22°C Fasciola hepatica
0.28
-
Boc-Asp-Pro-Arg-4-methyl-7-amidocoumarin pH 6.0, 22°C Homo sapiens
0.51
-
N-benzyloxycarbonyl-Val-Ile-Arg-4-methylcoumarin 7-amide pH 6.0, 22°C Fasciola hepatica
0.69
-
Boc-Asp-Pro-Arg-4-methylcoumarin 7-amide pH 6.0, 22°C Fasciola hepatica
0.72
-
Boc-Val-Pro-Arg-4-methylcoumarin 7-amide pH 6.0, 22°C Fasciola hepatica
1.09
-
N-benzyloxycarbonyl-Arg-Arg-4-methyl-7-amidocoumarin pH 6.0, 22°C Homo sapiens
1.71
-
N-benzyloxycarbonyl-Phe-Arg-4-methyl-7-amidocoumarin pH 6.0, 22°C Homo sapiens
2.26
-
Tos-Gly-Pro-Arg-4-methyl-7-amidocoumarin pH 6.0, 22°C Homo sapiens
3.38
-
Boc-Val-Leu-Lys-4-methyl-7-amidocoumarin pH 6.0, 22°C Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
4.5
-
autoprocessing Fasciola hepatica
5.5 7 catB1shows optimal activity within this range Fasciola hepatica
6
-
hydrolytic assay at Homo sapiens

pH Range

pH Minimum pH Maximum Comment Organism
4 8 FhcatB1is active across a broad pH range, approximately 30-80% of maximal activity at pH 5.0 and pH 8.0 Fasciola hepatica
4 8.5
-
Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
additional information
-
additional information rates of association of cysteine protease inhibitors with catB1, overview Fasciola hepatica
0.000093
-
Human cystatin C pH 6.0, 22°C Fasciola hepatica
0.000215
-
sheep cystatin B pH 6.0, 22°C Fasciola hepatica
0.000225
-
human cystatin A pH 6.0, 22°C Fasciola hepatica
0.0022
-
human cystatin B pH 6.0, 22°C Fasciola hepatica

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0000006
-
pH 6.0, 22°C Homo sapiens Human cystatin C
0.00037
-
pH 6.0, 22°C Homo sapiens human cystatin A
0.00041
-
pH 6.0, 22°C Homo sapiens sheep cystatin B

General Information

General Information Comment Organism
physiological function the FhcatB1 protease functions largely as a digestive enzyme in the gut of the parasite. It may be likely important to a vital stage of the parasite's life cycle Fasciola hepatica

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.032
-
D-Val-Leu-Arg-4-methylcoumarin 7-amide pH 6.0, 22°C Fasciola hepatica
0.244
-
Boc-Asp-Pro-Arg-4-methyl-7-amidocoumarin pH 6.0, 22°C Homo sapiens
1.046
-
N-benzyloxycarbonyl-Phe-Arg-4-methylcoumarin 7-amide pH 6.0, 22°C Fasciola hepatica
1.293
-
N-benzyloxycarbonyl-Arg-Arg-4-methylcoumarin 7-amide pH 6.0, 22°C Fasciola hepatica
1.346
-
Boc-Val-Pro-Arg-4-methylcoumarin 7-amide pH 6.0, 22°C Fasciola hepatica
1.976
-
Boc-Asp-Pro-Arg-4-methylcoumarin 7-amide pH 6.0, 22°C Fasciola hepatica
2.2
-
Boc-Val-Leu-Lys-4-methyl-7-amidocoumarin pH 6.0, 22°C Homo sapiens
2.227
-
Tos-Gly-Pro-Arg-4-methylcoumarin 7-amide pH 6.0, 22°C Fasciola hepatica
2.56
-
Tos-Gly-Pro-Arg-4-methyl-7-amidocoumarin pH 6.0, 22°C Homo sapiens
7.104
-
N-benzyloxycarbonyl-Val-Ile-Arg-4-methylcoumarin 7-amide pH 6.0, 22°C Fasciola hepatica
10.54
-
N-benzyloxycarbonyl-Arg-Arg-4-methyl-7-amidocoumarin pH 6.0, 22°C Homo sapiens
36.59
-
N-benzyloxycarbonyl-Phe-Arg-4-methyl-7-amidocoumarin pH 6.0, 22°C Homo sapiens