Naturally occurring inhibitors of intracellular proteinases

Abstract

The papain inhibitor isolated from chicken egg white inhibits the enzymatic activity of cathepsin B1 and cathepsin C. The inhibitor bears two nonoverlapping reactive sites: one binds cathepsin B1, papain, ficin, and bromelain, the other one cathepsin C. The inhibitor decreases the degree of an immunologic hypersensitive reaction, the so-called Arthus reaction. A statistically significant inhibition of this immunologically developed inflammation occurs only if the inhibitor is applied intradermally and simultaneously with the provoking dose of the antigen to rabbits sensitized to the same antigen. The pepsin inhibitor from the body walls of the roundworm Ascaris lumbricoides inhibits the proteolytic activity of cathepsin E. This inhibitor covalently bound to Sepharose 4B was used for affinity chromatography of cathepsin E. A cathepsin D inhibitor was isolated from potato tubers and its inhibitory and chemical characteristics were studied. The inhibitor does not inhibit either cathepsin E or pepsin yet inhibits trypsin in the alkaline pH-range. The molecular weight of the inhibitor is 21 790 and its molecule consists of 199 amino acid residues. The sequence of 17 amino acid residues was determined by Edman degradation of the inhibitor molecule.