The Effect of Divalent Cations on the Conformation and Function of Human Plasminogen.

The activation of native human plasminogen (Glu1-Pg) by tissue plasminogen activator,urinary plasminogen activator (u-PA),and streptokinase is inhibited by the divalent cations Ca2+,Mg2+,and Mn2+. This inhibition is accompanied by a conformational change in the molecule as evidenced by a decrease in Stokes' radius and intrinsic fluorescence. Kinetic analysis indicates that Mn2+ acts as an uncompetitive inhibitor of u-PA-catalyzed Glu1-Pg activation. In contrast to the inhibitory effects of divalent cations on Glu1-Pg,Ca2+ and Mg2+ stimulate the activation of proteolytically modified Lys77-Pg. These observations provide further evidence that Glu1-Pg and Lys77-Pg exhibit differential responses to ligands in the microenvironment.