INTERACTIONS OF ALPHA-1-ANTICHYMOTRYPSIN, ALPHA-1-PROTEINASE INHIBITOR, AND ALPHA-2-MACROGLOBULIN WITH THE FUNGAL ENZYME, SEAPROSE

The Semi-alkaline proteinase (Seaprose) from Aspergillus melleus has b een tested for its ability to either inactivate or form complexes with three human plasma proteinase inhibitors, alpha-2-macroglobulin, alph a-1-antichymotrypsin and alpha-1-proteinase inhibitor. alpha-2-Macrogl obulin was found to inhibit Seaprose, with two mol of enzyme being com plexed per mol of inhibitor. However, alpha-1-proteinase inhibitor was rapidly inactivated by the fungal enzyme as a result of cleavage of t he inhibitor, primarily at the P-1-P-1' reactive site. Curiously, alph a-1-antichymotrypsin was found to form complexes with Seaprose and als o be inactivated by this inhibitor. Apparently, the enzyme can recogni ze two sites within the reactive site loop of the inhibitor, one at th e P-4-P-5' position, resulting in inactivation, and one presumably at the P-1-P-1' reactive site which results in complex formation. The fac t that Seaprose can so rapidly inactivate alpha-1-proteinase inhibitor , the primary regulator of neutrophil elastase, indicates that Seapros e would be a rather poor choice for therapy in individuals with bronch ial mucus hypersecretion.