Enhanced plasminogen activation by staphylokinase in the presence of streptokinase beta/betagamma domains: plasminogen kringles play a role.
Presence of isolated beta or betagamma domains of streptokinase (SK) increased the catalytic activity of staphylokinase (SAK)-plasmin (Pm) complex up to 60%. In contrast, fusion of SK beta or betagamma domains with the C-terminal end of SAK drastically reduced the catalytic activity of the activator complex. The enhancement effect mediated by beta or betagamma 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 beta or betagamma domains) significantly. When catalytic activity of SAK-microPm (catalytic domain of Pm lacking kringle domains) complex was examined in the presence of isolated beta and betagamma domains, no enhancement effect on Pg activation was observed, whereas, enzyme complex formed between microplasmin and SAK fusion proteins (SAKbeta and SAKbetagamma) displayed 50-70% reduction in their catalytic activity. The present study, thus, suggests that the exogenously present beta and betagamma interact with Pg/Pm via kringle domains and elevate catalytic activity of SAK-Pm activator complex resulting in enhanced substrate Pg activation. Fusion of beta or betagamma domains with SAK might alter these intermolecular interactions resulting in attenuated functional activity of SAK.
Dahiya
Monika
M
Institute of Microbial Technology, Sector 39-A, Chandigarh 160036, India.
Rajamohan
G
G
Dikshit
Kanak L
KL
D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D007700:Kinetics; D018082:Kringles; D008666:Metalloendopeptidases / Q000378:metabolism*; D010958:Plasminogen / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013300:Streptokinase / Q000737:chemistry* / Q000378:metabolism
D011993:Recombinant Fusion Proteins; D010958:Plasminogen; D013300:Streptokinase; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus