title: Fasciola hepatica cathepsin L proteinase cleaves fibrinogen and produces a novel type of fibrin clot.
abstract: A cathepsin L proteinase secreted by the parasitic helminth Fasciola hepatica can cleave fibrinogen and produce a fibrin clot with a specific activity of 4.7 National Institutes of Health thrombin-equivalent U/mg. This is the first report of a fibrinogen-clotting activity aside that of thrombin and the snake venom proteinases, which are all serine proteinases. Clot formation by cathepsin L is not inhibited by the thrombin inhibitor hirudin or by the anti-polymerant H-Gly-Pro-Arg-Pro-OH. The enzyme exerts its activity on fibrinogen in a unique manner. Although the cleavage of fibrinogen may involve the initial removal of fibrinopeptides, additional proteolysis of the alpha, beta and gamma fibrinogen polypeptides takes place. SDS/PAGE analysis of the cathepsin-L-produced clots revealed that cleavage of the alpha polypeptide (66 kDa) precedes that of the beta (52 kDa) and gamma (46.5 kDa) polypeptides. Concurrent with the cleavage of these polypeptides is the appearance of components of 120, 100 and 25 kDa. The appearance of higher molecular-sized components in the cathepsin L clots suggests that polymerisation involves the formation of molecular interactions that are resistant to boiling in mercaptoethanol and SDS.
authors.affiliation: School of Biological Sciences, Dublin City University, Ireland.
authors.forename: A J
authors.initials: AJ
authors.lastname: Dowd
authors.forename: S
authors.initials: S
authors.lastname: McGonigle
authors.forename: J P
authors.initials: JP
authors.lastname: Dalton
mesh_terms: D000818:Animals; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism*; D002417:Cattle; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D010450:Endopeptidases; D005210:Fasciola hepatica / Q000201:enzymology*; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006629:Hirudins / Q000494:pharmacology; D010449:Peptide Mapping
chemical_list: D006629:Hirudins; D005337:Fibrin; D005340:Fibrinogen; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D056668:Cathepsin L