Recombinant human procathepsin S is capable of autocatalytic processing at neutral pH in the presence of glycosaminoglycans.
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.
Vasiljeva
Olga
O
Department of Biochemistry and Molecular Biology, Jozef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia.
Dolinar
Marko
M
Pungercar
Jerica Rozman
JR
Turk
Vito
V
Turk
Boris
B
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
D004792:Enzyme Precursors; D006025:Glycosaminoglycans; D011994:Recombinant Proteins; D002403:Cathepsins; C028217:cathepsin S