title: Recombinant human procathepsin S is capable of autocatalytic processing at neutral pH in the presence of glycosaminoglycans.
abstract: Cathepsin S is unique among mammalian cysteine cathepsins in being active and stable at neutral pH. We show that autocatalytic activation of procathepsin S at low pH is a bimolecular process that is considerably accelerated (approximately 20-fold) by glycosaminoglycans and polysaccharides such as dextran sulfate, chondroitin sulfates A and E, and dermatan sulfate through electrostatic interaction with the proenzyme. Procathepsin S is also shown to undergo autoactivation at neutral pH in the presence of dextran sulfate with t1/2 of approximately 20 min at pH 7.5. This novel property of procathepsin S may have implications in pathological conditions associated with the appearance of active cathepsins outside lysosomes.
authors.affiliation: Department of Biochemistry and Molecular Biology, Jozef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia.
authors.forename: Olga
authors.initials: O
authors.lastname: Vasiljeva
authors.forename: Marko
authors.initials: M
authors.lastname: Dolinar
authors.forename: Jerica Rozman
authors.initials: JR
authors.lastname: Pungercar
authors.forename: Vito
authors.initials: V
authors.lastname: Turk
authors.forename: Boris
authors.initials: B
authors.lastname: Turk
mesh_terms: D002384:Catalysis / Q000187:drug effects; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism*; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009994:Osmolar Concentration; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004792:Enzyme Precursors; D006025:Glycosaminoglycans; D011994:Recombinant Proteins; D002403:Cathepsins; C028217:cathepsin S