Lactacystin, a specific inhibitor of the proteasome, inhibits human platelet lysosomal cathepsin A-like enzyme.
Lactacystin, the most specific inhibitor of the proteasome, strongly inhibited at pH 5.5 the activity of human platelet lysosomal cathepsin A-like enzyme. At a concentration as low as 1-5 microM it almost completely decreased the hydrolysis rate of cathepsin A specific substrates: Cbz-Phe-Ala and FA-Phe-Phe. This inhibition was probably due to the lactacystin intermediate beta-lactone formed during 10 min hydrolysis at pH 8.0 since nonhydrolyzed inhibitor did not affect cathepsin A activity. Basing on similarities in the inhibitor sensitivity, pH optimum, and substrate preferences it is suggested that the cathepsin A-like activity may be involved in chymotrypsin-like activity of the proteasome.
Ostrowska
H
H
Department of Instrumental Analysis, Medical Academy, Bialystok, Poland.
Wojcik
C
C
Omura
S
S
Worowski
K
K
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors*; D002384:Catalysis; D043402:Cathepsin A; D003546:Cysteine Endopeptidases / Q000187:drug effects*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008247:Lysosomes / Q000187:drug effects* / Q000201:enzymology; D009097:Multienzyme Complexes / Q000187:drug effects*; D046988:Proteasome Endopeptidase Complex
D015853:Cysteine Proteinase Inhibitors; D009097:Multienzyme Complexes; C067713:lactacystin; D002268:Carboxypeptidases; C468629:CTSA protein, human; D043402:Cathepsin A; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine