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.