Fibrinolysis with des-kringle derivatives of plasmin and its modulation by plasma protease inhibitors

Biochemistry
E KomorowiczRaymund Machovich

Abstract

Quantitative characterization of the interaction of des-kringle1-5-plasmin (microplasmin) with fibrin(ogen) and plasma protease inhibitors may serve as a tool for further evaluation of the role of kringle domains in the regulation of fibrinolysis. Comparison of fibrin(ogen) degradation products yielded by plasmin, miniplasmin (des-kringle1-4-plasmin), microplasmin, and trypsin on SDS gel electrophoresis indicates that the differences in the enzyme structure result in different rates of product formation, whereas the products of the four proteases are very similar in molecular weight. Kinetic parameters show that plasmin is the most efficient enzyme in fibrinogen degradation, and the kcat/KM ratio decreases in parallel with the loss of the kringle domains. The catalytic sites of the four proteases have similar affinities for fibrin (KM values between 0.12 and 0.21 microM). Trypsin has the highest catalytic constant for fibrin digestion (kcat = 0.47 s-1), and among plasmins with different kringle structures, the loss of kringle5 results in a markedly lower catalytic rate constant (kcat = 0.0076 s-1 for microplasmin vs 0.048 s-1 for miniplasmin and 0.064 s-1 for plasmin). In addition, microplasmin is inactivated by plasmin inhibit...Continue Reading

References

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Citations

Apr 23, 2004·Trends in Pharmacological Sciences·Valery V NovokhatnyThomas P Zimmerman
Dec 13, 2000·Thrombosis Research·G VörösR Machovich
Jan 8, 2013·The Journal of Biological Chemistry·Colin LongstaffKrasimir Kolev
Jun 2, 2009·Journal of Vascular and Interventional Radiology : JVIR·Imo E HoeferJoris I Rotmans
Aug 23, 2008·Thrombosis Research·Valery Novokhatny
Jan 22, 2011·Journal of Thrombosis and Haemostasis : JTH·I VarjúK Kolev
Sep 12, 2015·Blood·Woosuk S HurChristian J Kastrup
Dec 10, 2003·The Journal of Biological Chemistry·Masahide KashiwagiHideaki Nagase
Aug 2, 2017·BioMed Research International·Anna Tanka-SalamonKrasimir Kolev
Mar 13, 2003·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Martin Ries, Martin Zenker
Jun 8, 2021·HemaSphere·Robert L Medcalf, Charithani B Keragala

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