Literature summary for 3.4.22.B60 extracted from

Stack, C.M.; Caffrey, C.R.; Donnelly, S.M.; Seshaadri, A.; Lowther, J.; Tort, J.F.; Collins, P.R.; Robinson, M.W.; Xu, W.; McKerrow, J.H.; Craik, C.S.; Geiger, S.R.; Marion, R.; Brinen, L.S.; Dalton, J.P.
Structural and functional relationships in the virulence-associated cathepsin L proteases of the parasitic liver fluke, Fasciola hepatica (2008), J. Biol. Chem., 283, 9896-9908.

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Cloned(Commentary)

Cloned (Comment)	Organism
recombinantly expressed in Pichia pastoris	Fasciola hepatica

Inhibitors

Inhibitors	Comment	Organism	Structure
benzyloxycarbonyl-Phe-Ala-diazomethyl ketone	FheCL2	Fasciola hepatica
cathepsin K inhibitor II	FheCL2	Fasciola hepatica

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism	Structure
0.0014	-	benzyloxycarbonyl-L-Leu-L-Arg-4-methylcoumarinyl-7-amide	FheCL2	Fasciola hepatica
0.0153	-	tosyl-Gly-Pro-Arg-4-methylcoumarinyl-7-amide	FheCL2	Fasciola hepatica
0.0337	-	tert-butoxycarbonyl-Gly-Pro-Arg-4-methylcoumarinyl-7-amide	FheCL2	Fasciola hepatica
0.04	-	benzyloxycarbonyl-L-Phe-L-Arg-4-methylcoumarinyl-7-amide	FheCL2	Fasciola hepatica
0.084	-	benzyloxycarbonyl-L-Pro-L-Arg-4-methylcoumarinyl-7-amide	FheCL2	Fasciola hepatica

Organism

Organism	UniProt	Comment	Textmining
Fasciola hepatica	Q24940	-	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
proteolytic modification	FhCL2 is expressed as 37000 Da zymogen that autocatalytically processes at pH 4.5 to produce a 24500 Da mature enzyme	Fasciola hepatica

Purification (Commentary)

Purification (Comment)	Organism
recombinant zymogen of cathepsin L2	Fasciola hepatica

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
benzyloxycarbonyl-L-Leu-L-Arg-4-methylcoumarinyl-7-amide + H2O	FhCL2	Fasciola hepatica	benzyloxycarbonyl-L-Leu-L-Arg + 7-amino-4-methylcoumarin	-	?
benzyloxycarbonyl-L-Phe-L-Arg-4-methylcoumarinyl-7-amide + H2O	FhCL2	Fasciola hepatica	benzyloxycarbonyl-L-Phe-L-Arg + 7-amino-4-methylcoumarin	-	?
benzyloxycarbonyl-L-Pro-L-Arg-4-methylcoumarinyl-7-amide + H2O	FhCL2	Fasciola hepatica	benzyloxycarbonyl-L-Pro-L-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	Fasciola hepatica	?	-	?
additional information	FheCL1 and FheCL2 exhibit similar preferences for amino acids at P1. Both enzymes have a clear preference for Arg at P1 position, but other residues accommodate in this position include Lys, Glu, Thr, and Met. These are all cleaved at similar relative rates to that observed for human cathepsin L and cathepsin K. FheCL1 and FheCL2 are similar to cathepsin K with regard to their preference for a P2 position Leu over Phe (human cathepsin L has a preference for P2 position 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	Fasciola hepatica	?	-	?
tert-butoxycarbonyl-Gly-Pro-Arg-4-methylcoumarinyl-7-amide + H2O	FhCL2	Fasciola hepatica	tert-butoxycarbonyl-Gly-Pro-Arg + 7-amino-4-methylcoumarin	-	?
tosyl-Gly-Pro-Arg-4-methylcoumarinyl-7-amide + H2O	FhCL2	Fasciola hepatica	tosyl-Gly-Pro-Arg + 7-amino-4-methylcoumarin	-	?

Synonyms

Synonyms	Comment	Organism
FhCL2	-	Fasciola hepatica

Turnover Number [1/s]

Turnover Number Minimum [1/s]	Turnover Number Maximum [1/s]	Substrate	Comment	Organism	Structure
1.17	-	tosyl-Gly-Pro-Arg-4-methylcoumarinyl-7-amide	FheCL2	Fasciola hepatica
1.62	-	benzyloxycarbonyl-L-Leu-L-Arg-4-methylcoumarinyl-7-amide	FheCL2	Fasciola hepatica
1.7	-	benzyloxycarbonyl-L-Phe-L-Arg-4-methylcoumarinyl-7-amide	FheCL2	Fasciola hepatica
2.48	-	tert-butoxycarbonyl-Gly-Pro-Arg-4-methylcoumarinyl-7-amide	FheCL2	Fasciola hepatica
2.64	-	benzyloxycarbonyl-L-Pro-L-Arg-4-methylcoumarinyl-7-amide	FheCL2	Fasciola hepatica

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism	Structure
0.000023	-	cathepsin K inhibitor II	FheCL2	Fasciola hepatica
0.00167	-	benzyloxycarbonyl-Phe-Ala-diazomethyl ketone	FheCL2	Fasciola hepatica

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Release 2023.1 (January 2023)