Interactions of α-1-Antichymotrypsin, a-1 -Proteinase Inhibitor, and a-2-Macroglobulin with the Fungal Enzyme, Seaprose

The Semi-alkaline proteinase (Seaprose) from Aspergillus melleus has been tested for its ability to either inactivate or form complexes with three human plasma proteinase inhibitors, a-2-macroglobulin, a-1-antichymotrypsin and a-1-proteinase inhibitor. a-2-Macroglobulin was found to inhibit Seaprose, with two mol of enzyme being complexed per mol of inhibitor. How-ever, a-1-proteinase inhibitor was rapidly inactivated by the fungal enzyme as a result of cleavage of the inhibitor primarily at the Pi-Pi reactive site. Curiously, a-1-antichymotrypsin was found to form complexes with Seaprose and also be inactivated by this inhibitor. Apparently, the enzyme can recognize two sites within the reactive site loop of the inhibitor, one at the P4-P5 position, resulting in inactivation, and one presumably at the Pi-P{ reactive site which results in complex for-mation. The fact that Seaprose can so rapidly inactivate a-1-proteinase inhibitor, the primary regulator of neutrophil elastase, indicates that Seaprose would be a rather poor choice for therapy in individuals with bronchial mucus hypersecretion.