Effects of N-terminal peptide of Glu-plasminogen on the activation of Glu-plasminogen and its conversion to Lys-plasminogen.
In order to analyze the mechanism of the intramolecular binding of the N-terminal peptide of Glu-plasminogen (Glu-plg) to its kringles, which results in its tight conformation, we synthesized peptides of the N-terminal portion of Glu-plg molecules and analyzed their effects on the activation of Glu-plg and its conversion to Lys-plasminogen (Lys-plg) by plasmin. Three peptides of Ala44-Lys50, Ala44-Glu51 and Ala44-Ser49 were synthesized in order to examine the effect of lysine residue in the peptide. Ala44-Lys50 and Ala44-Glu51 enhanced the activation of Glu-plg by urokinase, whereas the activation of Lys-plasminogen (Lys-plg) was slightly inhibited. The conversion of Glu-plg to Lys-plg by plasmin was also enhanced by these peptides. The results suggest that Ala44-Lys50 and Ala44-Glu51 worked on Glu-plg in a similar manner as lysine analogues by making its conformation looser. The third peptide Ala44-Ser49 did not have any effect on the activation of Glu-plg by urokinase or the conversion of Glu-plg to Lys-plg by plasmin. Ala44-Lys50 residue of Glu-plg is, therefore, strongly implicated as a candidate for the responsible site of the intramolecular binding in Glu-plg.
Department of Physiology, Hamamatsu University School of Medicine, Shizuoka-ken, Japan.
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Urano
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Takada
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Takada
D000409:Alanine; D000595:Amino Acid Sequence; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D005971:Glutamates; D018698:Glutamic Acid; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010958:Plasminogen / Q000187:drug effects* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D013053:Spectrophotometry
D005971:Glutamates; D010446:Peptide Fragments; D010455:Peptides; C018998:lysyl-plasminogen; D018698:Glutamic Acid; D010958:Plasminogen; D000409:Alanine