Mechanism of Activation of Human Plasminogen by Streptokinase

The role of proactivators for the streptokinase activation of human plasminogen was studied. It was found that plasmin, as well as plasminogen, can form activator complex with streptokinase. The relative importance of these two proactivators for the streptokinase activation of human plasminogen is discussed. The use of the active center-specific reagent, p-nitrophenyl-p-guanidinobenzoate (NPGB) established that an active center appears in the streptokinase-plasminogen complex even before proteolytic activity develops, i.e. before conversion to streptokinase-plasmin. When, in the presence of NPGB, plasminogen is mixed with increasing amounts of streptokinase, equivalent amounts of unactivatable plasminogen are obtained. Physical evidence indicates that the active center develops in the complex before the plasminogen moiety was converted to plasmin, i.e. before cleavage of the single peptide chain of plasminogen. Activator activity, like NPGB-reactivity, is imparted to the complex before proteolytic activity is acquired. It appears that the transitory streptokinase-plasminogen complex plays a dominant role in the streptokinase activation of human plasminogen, as its formation does not depend on the presence of spontaneous plasmin.