Cathepsin L

CA C1 C01.033 Cathepsin L-like peptidase (Fasciola sp.) Potential drug target for liver fluke infection... 

Gener ally, a family of peptidases contains either exopeptidases or endopeptidases, but there are exceptions. Family Cl contains not only endopeptidases such as cathepsin L, but also the aminopeptidase bleomycin hydrolase. Some members of this family can act as exopeptidases as well as endopeptidases. For example, cathepsin B also acts as a peptidyl-dipeptidase, and... 

Cleavage occur s at the scissile bond. Residues in the substrate towards the N-terminus are numbered PI, P2, P3, etc, whereas residues towards the C-terminus are numbered PI, P2, P3 etc. Cleavage occurs between PI and P1. For a peptidase with limited specificity, only the residue in PI or PI is important for specificity. A peptidase with an extended substrate binding site will have a preference for residues in other positions. For example cathepsin L prefers substrates with phenylalanine in P2 and arginine in PI. However, this is a preference only, and cathepsin L cleaves substrates after other amino acids. Caspase-3 has a preference for Asp in both P4 and PI, but it is unusual for substrate specificity to extend much further from the scissile bond. The peptidase with the most extended substrate specificity may be mitochondrial intermediate peptidase that removes an octopeptide targeting signal from the N-terminus of cytoplasmically synthesized proteins that are destined for import into the mitochondrial lumen. 

Loukas, A., Selzer, P.M. and Maizels, R.M. (1998) Characterisation of Tc-cpl-1, a cathepsin L-like cysteine protease from Toxocara canis infective larvae. Molecular and Biochemical Parasitology 92, 275—289. 

Dalton, J.P., McGonigle, S., Rolph, T.P. and Andrews, S.J. (1996) Induction of protective immunity in cattle against infection with Fasciola hepatica by vaccination with cathepsin L proteases and haemoglobin. Infection and Immunity 64, 5066-5074. 

Piacenza L., Acosta, D., Basmadjan, I., Dalton, J.P. and Carmona, C. (1999) Vaccination with cathepsin L proteases and with leucine aminopeptidase induces high levels of protection against fascioliasis in sheep. Infection and Immunity 67, 1954-1961. 

Rhoads, M.L. and Fetterer, R.H. (1995) Developmentally regulated secretion of cathepsin L-like proteases by Haemonchus contortus. Journal for Parasitology 81, 505-512. 

Shimizu, K., Cha, J., Stucky, G.D. and Morse, D.E. (1998) Silicatein alpha Cathepsin L-like protein in sponge biosilica. Proceedings of the National Academy of Sciences of the United States of America, 95, 6234-6238. 

This lysosomal enzyme [EC 3.4.22.1], also known as cathepsin Bl, is a member of the peptidase family Cl. The catalyzed reaction is the hydrolysis of peptide binds with a broad specificity. The enzyme prefers the ArgArg—Xaa bond in small peptide substrates (thus distinguishing this enzyme from cathepsin L). The enzyme also exhibits a peptidyl-dipeptidase activity, releasing C-terminal dipeptides from larger polypeptides. 

This peptidase family Cl enzyme [EC 3.4.22.15] is an lysosomal endopeptidase with specificity akin to papain. Cathepsin L displays a higher activity toward protein substrates than does cathepsin B. 

OATENARY MODEL FOR COMPARTMENT ANALYSIS OATHEPSIN B OATHEPSIN D CATHEPSIN E OATHEPSIN G CATHEPSIN H CATHEPSIN L CATHEPSIN S CATHEPSIN T... 

Proteins papain/cathepsin-L protease fonily (Mar spicules of Tethya aurantia, Porif. from California Shimizu 1998 Land kidney of Mamm. and tropical fruits of Ang. MI). 

Figure B3.1.1 A 15% SDS-polyacrylamide gel stained with Coomassie brilliant blue. Protein samples were assayed for the purification of a proteinase, cathepsin L, from fish muscle according to the method of Seymour et al. (1994). Lane 1, purified cathepsin L after butyl-Sepharose chromatography. Lane 2, cathepsin L complex with a cystatin-like proteinase inhibitor after butyl-Sepharose chromatography. Lane 3, sarcoplasmic fish muscle extract after heat treatment and ammonium sulfate precipitation. Lane 4, sarcoplasmic fish muscle extract. Lanes M, low-molecular-weight standards aprotinin (Mr 6,500), a-lactalbumin (Mr 14,200), trypsin inhibitor (Mr 20,000), trypsinogen (Mr 24,000), carbonic anhydrase (Mr 29,000), gylceraldehyde-3-phosphate dehydrogenase (Mr 36,000), ovalbumin (Mr 45,000), and albumin (Mr 66,000) in order shown from bottom of gel. Lane 1 contains 4 pg protein lanes 2 to 4 each contain 7 pg protein.

It is interesting that within the cathepsin L clade of Fasciola, significant allelic diversification has taken place. Thus far, 6 and 1 7 different cathepsin L sequences have been identified for F. gigantica and F. hepatica, respectively, but all belong to a mono-... 

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