Preetpal Singh Sidhu. Journal of Pharmacy and Pharmacology 1 (2013) 1-10. Abstract: Thrombin is the most important and highly targeted protease in coagulation cascade to develop anticoagulation therapy. It has dual function in coagulation system and highly regulated by allosteric mode. Based on binding by various protein and peptides in exosite 1 and 2, it […]
View Post Anticoagulant, procoagulant, ThrombinRuf W, Ruggeri ZM. Nat Med. 2010 Aug;16(8):887-96. Blood coagulation protects from microbial infections. A recent study now shows that neutrophils fine tune the procoagulant response to invading pathogens. Neutrophils degrade an inhibitor of coagulation, locally ‘trapping’ bacteria in small blood vessels. But they also increase blood clots in large vessels in the absence of infection, […]
View Post coagulation, microbial infections, neutrophils, procoagulantMüller F, Mutch NJ, Schenk WA, Smith SA, Esterl L, Spronk HM, Schmidbauer S, Gahl WA, Morrissey JH, Renné T. Cell. 2009 Dec 11;139(6):1143-56. Platelets play a central role in thrombosis, hemostasis, and inflammation. We show that activated platelets release inorganic polyphosphate (polyP), a polymer of 60-100 phosphate residues that directly bound to and activated the plasma protease factor XII. PolyP-driven factor XII activation triggered […]
View Post bradykinin, kallikrein, procoagulant, pulmonary embolism, thrombosisGruber A, Cantwell AM, Di Cera E, Hanson SR. J Biol Chem. 2002 Aug 2;277(31):27581-4. Epub 2002 Jun 17. Administration of the thrombin mutant W215A/E217A (WE), rationally designed for selective activation of the anticoagulant protein C, elicits safe and potent anticoagulant and antithrombotic effects in a baboon model of platelet-dependent thrombosis. The lowest dose of WE tested (0.011 mg/kg […]
View Post Anticoagulant, antithrombotic, E217A, procoagulant, Protein C, W215A, W215A/E217ADi Cera E. J Thromb Haemost. 2007 Jul;5 Suppl 1:196-202. Thrombin is a Na(+)-activated, allosteric serine protease that plays opposing functional roles in blood coagulation. Binding of Na(+) is the major driving force behind the procoagulant, prothrombotic and signaling functions of the enzyme, but is dispensable for cleavage of the anticoagulant protein C. This basic regulatory […]
View Post Anticoagulant, Anticoagulation, coagulation, fibrinogen, procoagulant, thrombin generationCantwell AM, Di Cera E. J Biol Chem. 2000 Dec 22;275(51):39827-30. Thrombin acts as a procoagulant when it cleaves fibrinogen and promotes the formation of a fibrin clot and functions as an anticoagulant when it activates protein C with the assistance of the cofactor thrombomodulin. The dual function of thrombin in the blood poses the challenge to […]
View Post fibrin clot, fibrinogen, procoagulant, Protein C, Thrombin, W215A/E217ABouma BN, Meijers JC. Curr Opin Hematol. 2000 Sep;7(5):266-72. Factor XI is a component of the intrinsic pathway of coagulation. A deficiency of factor XI is associated with a mild to moderate bleeding disorder especially from tissues with a high local fibrinolytic activity. In contrast, high levels of factor XI are a risk factor for venous thrombosis. […]
View Post coagulation, factor XI, fibrin formation, fibrinolysis, procoagulant, Thrombin, thrombin generation, VENOUS THROMBOSISLeung LL, Gibbs CS. Thromb Haemost. 1997 Jul;78(1):577-80. The procoagulant and anticoagulant functions of thrombin are controlled physiologically by allosteric changes induced by Na+ and vascular cell-surface TM. Key residues that mediate Na+ interaction with thrombin have been identified. Based on a site-directed mutagenesis approach, E229K thrombin is found to be the most optimal and potent PC […]
View Post Anticoagulant, antithrombotic, procoagulant, ThrombinGibbs CS, Coutré SE, Tsiang M, Li WX, Jain AK, Dunn KE, Law VS, Mao CT, Matsumura SY, Mejza SJ, et al. Nature. 1995 Nov 23;378(6555):413-6. At sites of vascular injury, thrombin interacts with multiple procoagulant substrates, to mediate both fibrin clotting and platelet aggregation. But upon binding to thrombomodulin on the vascular endothelium, thrombin instead activates protein C, thereby functioning as an anticoagulant and […]
View Post Anticoagulant, antithrombotic, fibrinogen, procoagulant, Protein C, ThrombinTsiang M, Jain AK, Dunn KE, Rojas ME, Leung LL, Gibbs CS. J Biol Chem. 1995 Jul 14;270(28):16854-63. Utilizing site-directed mutagenesis, 77 charged and polar residues that are highly exposed on the surface of human thrombin were systematically substituted with alanine. Functional assays using thrombin mutants identified residues that were required for the recognition and cleavage of the procoagulant substrate fibrinogen […]
View Post Anticoagulant, procoagulant, Thrombin