Antiplasmin, the Fast-Reacting Plasmin Inhibitor of Human Plasma

Recently a new plasmin inhibitor was discovered in human plasma by three different groups (Eur. J. Biochem. 69, 209, 1976; J. Biol. Chem. 251, 5956, 1976; Biochem. J. 159, 545, 1976). This inhibitor is responsible for the fast-reacting plasmin-neutraIizing activity of human plasma and forms a very stable 1:1 molar complex with plasmin, which is devoid of protease and esterase activity. The concentration of antiplasmin in human plasma is approximately I μM (2/3 that of plasminogen). We have purified the inhibitor by affinity chromatography on insolubilized plasminogen, followed by DEAE-Sephadex and concanavalin A chromatography. It is a glycoprotein with a mol . wt. of 67,000 (SDS-gel electrophoresis), a carbohydrate content of 14%, and amino terminal sequence Asn-Gln-Glu-Gly (Wiman and Collen, submitted). The inhibitor interacts strongly with the light chain of plasmin (probably through reaction with the active site serine), and weakly with the heavy chain (probably through interaction with the lysine-binding site), suggesting that antiplasmin not only functions as an inhibitor of plasmin, but also interferes with the interaction between plasm in (ogen) and fibrin.