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

The effect of various concentrations of -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 D₁(FD₁). In the absence of FD₁, 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), Lys₇₇-plasminogen (Lys₇₇-Pg), and Val₄₄₂-plasminogen (Val₄₄₂-Pg) at levels of EACA from 0–25 mM. In the presence of 2 μM FD₁, the k_obs for active site formation in the SK·Glu₁-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· Lys₇₇-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·Val₄₄₂-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 D₁ is mediated by sites separate from the lysine binding sites of plasminogen.