title: Regulation of the activity of lysosomal cysteine proteinases by pH-induced inactivation and/or endogenous protein inhibitors, cystatins.
abstract: The kinetics of pH-induced inactivation of human cathepsins B and L was studied by conventional and stopped-flow methods. The inactivation of both enzymes was found to be an irreversible, first-order process. The inactivation rate constants increased exponentially with pH for both enzymes. From log kinac vs pH plots, 3.0 and 1.7 protons were calculated to be desorbed for pH-induced inactivation of cathepsins L and B. Cathepsin B was thus substantially more stable than cathepsin L (approximately 15-fold at pH 7.0 and 37 degrees C). Cathepsin B was efficiently inhibited by cystatin C at pH 7.4, whereas the inhibition by stefin B and high molecular weight kininogen was only moderate. In contrast, cathepsin L was efficiently inhibited by both chicken cystatin and stefin B at this pH kass approximately 3.3 x 10(7) m-1 s-1).
authors.affiliation: Dept. Biochemistry and Molecular Biology, J. Stefan Institute, Ljubljana, Slovenia.
authors.forename: B
authors.initials: B
authors.lastname: Turk
authors.forename: J G
authors.initials: JG
authors.lastname: Bieth
authors.forename: I
authors.initials: I
authors.lastname: Björk
authors.forename: I
authors.initials: I
authors.lastname: Dolenc
authors.forename: D
authors.initials: D
authors.lastname: Turk
authors.forename: N
authors.initials: N
authors.lastname: Cimerman
authors.forename: J
authors.initials: J
authors.lastname: Kos
authors.forename: A
authors.initials: A
authors.lastname: Colic
authors.forename: V
authors.initials: V
authors.lastname: Stoka
authors.forename: V
authors.initials: V
authors.lastname: Turk
mesh_terms: D000818:Animals; D002401:Cathepsin B / Q000037:antagonists & inhibitors; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors; D002645:Chickens; D015891:Cystatins / Q000502:physiology*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D010450:Endopeptidases; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008247:Lysosomes / Q000201:enzymology*
chemical_list: D015891:Cystatins; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C028217:cathepsin S