The role of the lysine binding sites of human plasminogen in the fibrinogen stimulated rate of active site formation in the streptokinase-plasminogen equimolar complex

Abstract

The effect of various concentrations of ε-amino caproic acid (EACH) on the rate of active site formation in the human plasminogen moiety of the streptokinase-plasminogen equimolar complex has been studied in the absence and presence of human fibrinogen fragment D 1(FD 1). In the absence of FD 1, the pseudo first order rate constant (k obs) for active site development in this complex ranges from 8.4–17.9 × 10 −3 sec −1 with Glul-plasminogen (Glul-Pg), Lys 77-plasminogen (Lys 77-Pg), and Val 442-plasminogen (Val 442-Pg) at levels of EACA from 0–25 mM. In the presence of 2 μM FD 1, the k obs for active site formation in the SK·Glu 1-Pg complex, of 60.1 × 10 −3 sec −1, was not altered significantly as the EACA level was increased to 25 mM. Similarly, in the SK· Lys 77-Pg complex, the k obs for active site formation, of 62.1 × 10 −3 sec −1, was essentially unchanged as the EACA level was increased to 25 mM. Finally, the k obs for active site formation in the SK·Val 442-Pg complex, of 113.6 × 10 −3 sec −1, was also unaffected at levels of EACA up to 5 mM, with a slight inhibition at 25 mM EACA. These results show that the stimulation of active site formation in the equimolar SK·Pg complex by fibrinogen fragment D 1 is mediated by sites separate from the lysine binding sites of plasminogen.