Enhancement of the streptokinase-catalyzed activation of human plasminogen by human fibrinogen and its plasminolysis products

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Abstract
The effects of human fibrinogen, and several plasmin-derived fragments of fibrinogen, on the streptokinase-induced activation of human plasminogen (Pg) were investigated. Fibrinogen stimulates the rate of activation of human Glu1-Pg, Lys77-Pg, and Val442-Pg. The cofactor activity of fibrinogen appears to reside mainly in the D-domain region, since purified fragment D is active in this system. Fibrinogen fragment E was not active in this regard. The cofactor activity of fragment D was partially dependent on the presence of Ca2+. This effect of Ca2+ was likely due to its stabilizing influence on fragment D, as revealed by studies employing differential scanning calorimetry. Conversion of fragment D1 to fragments D2-5 did not alter the cofactor activity. Steady-state kinetic analysis of the activation of Val442-Pg by the streptokinase-Val442-plasmin complex demonstrated that the Km decreased approximately 2-fold, in the presence of fragment D1. Very little change in the steady-state kinetic parameters for Glu1-Pg and Lys77-Pg, when activated by the streptokinase-Lys77-plasmin complex, was noted in the presence of fragment D1. Both fibrinogen and fibrinogen fragment D1 increased the rate of formation of the active site in the streptokinase-Pg complex, of all forms of Pg. This effect was sufficient to explain the overall stimulation of the activation of Pg by fibrinogen and fibrinogen fragment D1.