Enhanced plasminogen activation by staphylokinase in the presence of streptokinase β/βγ domains: Plasminogen kringles play a role

Presence of isolated β or βγ domains of streptokinase (SK) increased the catalytic activity of staphylokinase (SAK)-plasmin (Pm) complex up to 60%. In contrast, fusion of SK β or βγ domains with the C-terminal end of SAK drastically reduced the catalytic activity of the activator complex. The enhancement effect mediated by β or βγ domain on Pg activator activity of SAK-Pm complex was reduced greatly (45%) in the presence of isolated kringles of Pg, whereas, kringles did not change cofactor activity of SAK fusion proteins (carrying β or βγ domains) significantly. When catalytic activity of SAK-microPm (catalytic domain of Pm lacking kringle domains) complex was examined in the presence of isolated β and βγ domains, no enhancement effect on Pg activation was observed, whereas, enzyme complex formed between microplasmin and SAK fusion proteins (SAKβ and SAKβγ) displayed 50-70% reduction in their catalytic activity. The present study, thus, suggests that the exogenously present β and βγ interact with Pg/Pm via kringle domains and elevate catalytic activity of SAK-Pm activator complex resulting in enhanced substrate Pg activation. Fusion of β or βγ domains with SAK might alter these intermolecular interactions resulting in attenuated functional activity of SAK.