Thrombin interaction with fibrin polymerization sites

Thrombosis Research
K Hsieh

Abstract

Thrombin is central to hemostasis, and postclotting fibrinolysis and wound healing. During clotting, thrombin transforms plasma fibrinogen into polymerizing fibrin, which selectively adsorbs the enzyme into the clot. This protects thrombin from heparin-antithrombin inactivation, thus preserving the enzyme for postclotting events. To determine how the fibrin N-terminal polymerization sites of A alpha 17-23 (GPRVVER) and B beta 15-25 (GHRPLDKKREE) and their analogs may interact with thrombin, amidolysis vs. plasma- and fibrinogen-clotting assays were used to differentiate blockade of catalytic site vs. other thrombin domains. Amidolysis studies suggest GPRVVER inhibition of thrombin catalytic site through hydrophobic interaction, and GPRVVER inhibited clotting. Neither GPRP nor VVER nor the B beta 15-25 homologs inhibited amidolysis. Contrary to heparin, acyl-DKKREE promoted plasma-clotting, but inhibited fibrinogen-clotting. In addition, acyl-DKKREE reversed the anticoagulant effect of heparin (0.1 U/ml) in plasma. The results suggest fibrin B beta 15-25 interaction with thrombin, possibly by blocking the heparin-binding site. Together with the reported fibrin A alpha 27-50 binding to thrombin, polymerizing fibrin appears to ini...Continue Reading

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Citations

Sep 27, 2003·Thrombosis Research·Jamal LebraziMeyer Michel Samama
Dec 19, 2002·Neurosurgery Clinics of North America·Guohua XiJulian T Hoff
Jan 25, 2002·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Ya HuaJulian T Hoff
Jun 5, 2002·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Yajun JiangGuohua Xi

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