The control of the urokinase-catalyzed activation of human glutamic acid 1-plasminogen by positive and negative effectors.

摘要: The urokinase-catalyzed activation of human Glu1-plasminogen (Glu1Pg) has been found to be inhibited by monovalent anions in the following order effectiveness: I- greater than SCN- Cl- IO3- HCOO- F- OAc-. inhibition is reversed epsilon-aminocaproic acid, with its effectiveness this capacity generally inversely proportional strength binding anion. physical basis for anion and acid stimulation lies ability these effectors cause measurable opposite alterations conformation Glu1Pg, which are revealed through study sedimentation velocity protein under various conditions. kinetic mechanism chloride Glu1Pg examined detail. It that Glu1Pg.Cl complex serves as an alternate substrate urokinase, a greatly increased Km (25 +/- 3 2.2 0.3 microM, respectively) activation. kcat urokinase.Glu1Pg.Cl approximately same urokinase.Glu1Pg (1.6 0.2 - 2.0 0.2/s). Similarly, also results from effects on activation, reduced 1.8 microM Glu1Pg.Cl.epsilon-aminocaproic complex. urokinase.Glu1Pg.Cl.epsilon-aminocaproic 2.4 0.3/s not different urokinase.Glu1Pg.Cl. Nuclear magnetic resonance studies Glu1Pg-induced line broadening 35Cl- spectra presence absence suggest simultaneously bind each displays separate sites.