PROTEASE-SPECIFICITY OF KUNITZ INHIBITOR DOMAIN OF ALZHEIMERS-DISEASE AMYLOID PROTEIN-PRECURSOR

The putative inhibitor domain of Alzheimer's disease amyloid protein precursor was purified from E. coli containing a synthetic gene encoding the Kunitz domain. The purified protein (A4 inhibitor) inhibited the activity of trypsin, forming a 1:1 molar complex with the enzyme. It also strongly inhibited plasmin (Ki = 7.5 × 10-11 M) from human serum and tryptase (Ki = 2.2 × 10-10 M) from rat mast cells (tryptase M). In addition, it inhibited rat pancreatic trypsin, α-chymotrypsin and kallikrein and human serum kallikrein, but did not inhibit rat chymase, pancreatic elastase, α-thrombin, urokinase, papain or cathepsin B. © 1990.