Protease-specificity of Kunitz inhibitor domain of Alzheimer's 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 x 10(-11) M) from human serum and tryptase (Ki = 2.2 x 10(-10) M) from rat mast cells (tryptase M). In addition, it inhibited rat pancreatic trypsin, alpha-chymotrypsin and kallikrein and human serum kallikrein, but did not inhibit rat chymase, pancreatic elastase, alpha-thrombin, urokinase, papain or cathepsin B.
Kido
H
H
Division of Enzyme Chemistry, University of Tokushima, Japan.
Fukutomi
A
A
Schilling
J
J
Wang
Y
Y
Cordell
B
B
Katunuma
N
N
D000595:Amino Acid Sequence; D000682:Amyloid / Q000235:genetics* / Q000494:pharmacology; D016564:Amyloid beta-Protein Precursor; D000818:Animals; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics; D005341:Fibrinolysin / Q000037:antagonists & inhibitors; D005813:Genes, Synthetic; D006801:Humans; D007700:Kinetics; D008407:Mast Cells / Q000201:enzymology; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics* / Q000494:pharmacology; D051381:Rats; D013379:Substrate Specificity; D014357:Trypsin / Q000378:metabolism; D014360:Trypsin Inhibitor, Kunitz Soybean / Q000235:genetics* / Q000494:pharmacology; D014361:Trypsin Inhibitors / Q000235:genetics*
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D011498:Protein Precursors; D014361:Trypsin Inhibitors; D014360:Trypsin Inhibitor, Kunitz Soybean; D010447:Peptide Hydrolases; C023073:tosylarginine methyl ester hydrolase; D014357:Trypsin; D005341:Fibrinolysin