DISTORTION OF THE ACTIVE-SITE OF CHYMOTRYPSIN COMPLEXED WITH A SERPIN

There is no complete understanding of how serine protease inhibitors o f the serpin family inhibit their target enzymes. Structural and bioch emical studies have suggested that serpins utilize a mechanism that is distinct from the standard mechanism of inhibition proposed for most small protein protease inhibitors. Proton nuclear magnetic resonance s pectroscopy was used in the present study to demonstrate a fundamental difference in the atomic environment of the catalytic triad of enzyme in complex with serpins when compared to uncomplexed enzyme and enzym e in complex with standard mechanism inhibitors. This work demonstrate s that the active site of chymotrypsin is distorted when complexed to a serpin and makes tenable a mechanism of inhibition in which the serp in induces a conformational change in the enzyme that dramatically red uces or completely abrogates the catalytic activity of the protease.