Poly-D-lysine dependent inactivation of tissue plasminogen activator by a class PAI-2 inhibitor (minactivin).
Two-chain tissue plasminogen activator (t-PA) was found to be inactive in a coupled colorimetric assay for plasminogen activators, but a high level of activity was obtained in the presence of poly-D-lysine. This stimulated activity was strongly inhibited by minactivin, a urokinase inhibitor, but unstimulated enzyme could be shown to be unaffected by minactivin. In the presence of poly-D-lysine minactivin was a very successful competitive inhibitor of t-PA with respect to the substrate, plasminogen. The Ki for minactivin determined by the Henderson method was 2.5 X 10(-12) M, compared to the Km for plasminogen determined as 0.6 X 10(-6) M. The value of Ki for minactivin with u-PA, determined under the same conditions, was 1.6 X 10(-11) M.
D004347:Drug Interactions; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015849:Plasminogen Inactivators; D011107:Polylysine / Q000494:pharmacology*; D011485:Protein Binding; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors*; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
D015849:Plasminogen Inactivators; C039812:minactivin; D011107:Polylysine; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator