Influence of cyanogen-bromide-digested fibrinogen on the kinetics of plasminogen activation by urokinase.
The catalytic efficiency (kcat/Km) of high-molecular-mass urokinase for the activation of Glu-plasminogen is increased about 10-fold in the presence of CNBr-digested fibrinogen. This stimulation is similar to that observed with 6-aminohexanoic acid, and yields kinetic parameters comparable to those for the activation of Lys-plasminogen by urokinase. The increase of the activation rate of Glu-plasminogen by urokinase in the presence of CNBr-Fg can thus be explained by a conformational change in the plasminogen molecule similar to that observed upon conversion of Glu-plasminogen to Lys-plasminogen and upon binding of 6-aminohexanoic acid to Glu-plasminogen. Stabilization of the Michaelis complex between urokinase and plasminogen by formation of a cyclic ternary complex with CNBr-Fg, which has been invoked to explain the dramatic stimulatory effect of CNBr-Fg on the activation of plasminogen by tissue-type plasminogen activator, does not appear to play a significant role in the increased activation rate.
D003488:Cyanogen Bromide / Q000494:pharmacology*; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D010446:Peptide Fragments / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism; D011487:Protein Conformation; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D010446:Peptide Fragments; C018998:lysyl-plasminogen; D005340:Fibrinogen; D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator; D003488:Cyanogen Bromide