Conformational change of plasminogen: effects of N-terminal peptides of Glu-plasminogen

Seven peptides were synthesized to analyze the mechanism of the intramolecular binding of the N-terminal peptide of Glu-plasminogen (Glu-plg) to its kringles. They were Ala44-Lys50, Ala44-Glu51, Ala44-Ser49, Val17-Gly23, Lys19-Gly23, Lys19-Gln21 and Lys19-Lys20. Ala44-Lys50, Ala44-Glu51 and Lys19-Lys20.enhanced the activation of Glu-plg by tissue plasminogen activator (t-PA) or urinary plasminogen activator (u-PA). The activation of Lys-plg, however, was not influenced by these peptides. Therefore, it is suggested that these three peptides worked on Glu-plg in a similar manner as lysine analogue by making the conformation of Glu-plg looser. These peptides did not have any direct effects on u-PA and t-PA. Concerning the effect on fibrinolysis Ala44-Lys50 and Lys19-Lys20 prolonged euglobulin clot lysis time. These results indicate that Ala44-Glu51 may be a responsible binding site in the N-terminal portion of Glu-plg, and LBS of kringle 1 or 4 is the binding site of N-terminal portion of Glu-plg.