Distortion of the active site of chymotrypsin complexed with a serpin.

There is no complete understanding of how serine protease inhibitors of the serpin family inhibit their target enzymes. Structural and biochemical 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 spectroscopy 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 enzyme in complex with standard mechanism inhibitors. This work demonstrates that the active site of chymotrypsin is distorted when complexed to a serpin and makes tenable a mechanism of inhibition in which the serpin induces a conformational change in the enzyme that dramatically reduces or completely abrogates the catalytic activity of the protease.