Specificity and Biological Role of Cathepsin D

Publisher Website
Google Scholar
Abstract
Cathepsin D was originally isolated from bovine spleen by Press, Porter and Cebra in 1960 (1). My interest in this enzyme was aroused by the observation of its high levels of activity in the involuting post-partum uterus (2); in fact, the uterus contains high levels of this enzyme even in the normal nongravid condition. This led to the purification of cathepsin D from the bovine uterus (3). Uterine cathepsin D was insensitive to a large number of inhibitors specific for thiol, serine, and metallo-proteases, and incapable of cleaving a large group of synthetic peptide substrates typically used for the known proteases (4). Strong inhibition could be obtained only by the use of heavy metals such as Pb2+ and Hg2+. The specificity was determined by the use of the S-sulfo B chain of insulin. Most rapid splitting was at the bonds Leu15-Tyr16, Phe24-Phe25 and Phe25-Tyr26; secondary splitting was found at G1u13-Ala14, and Tyr16-Leu17. These points of cleavage are the same as reported by Press et al. (1). Minor splits were also observed at Phel-Va12 and Ala14-Leu15 (4).