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.
Department of Physiology, Hamamatsu University, School of Medicine, Shizuoka-ken, Japan.
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Takada
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Urano
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Takada
D000595:Amino Acid Sequence; D001665:Binding Sites; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010958:Plasminogen / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology
D010446:Peptide Fragments; D011994:Recombinant Proteins; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator