Verbout NG, Yu X, Healy LD, Phillips KG, Tucker EI, Gruber A, McCarty OJ, Offner H. Metab Brain Dis. 2014 May 9 [Epub ahead of print]. Abstract: Multiple sclerosis (MS) is a neuroinflammatory disease characterized by demyelination and axonal damage of the central nervous system. The pathogenesis of MS has also been linked to vascular […]
View Post protein C activation, W215A/E217A, WE-thrombinVicente CP, Weiler H, Di Cera E,Tollefsen DM. Thromb Res. 2011 Dec 16. The thrombin mutant W215A/E217A (WE thrombin) has greatly reduced procoagulant activity, but it activates protein C in the presence of thrombomodulin and inhibits binding of platelet glycoprotein Ib to von Willebrand factor and collagen under flow conditions. Both thrombomodulin-dependent protein C activation […]
View Post E217A, protein C activation, von Willebrand factor, W215A/E217A, WE-thrombinDi Cera E. Prog Mol Biol Transl Sci. 2011;99:145-84. Thrombosis is the most prevalent cause of fatal diseases in developed countries. An antithrombotic agent that can be administered to patients with severe acute thrombotic diseases without the risk of causing hemorrhage, as experienced with antithrombotic/thrombolytic therapy in the treatment of acute ischemic stroke or systemic anticoagulants […]
View Post antithrombotic, ischemic stroke, protease-activated receptors, Protein C, protein C activation, thrombolytic therapy, thrombosisMarino F, Pelc LA, Vogt A, Gandhi PS, Di Cera E. J Biol Chem. 2010 Jun 18;285(25):19145-52. Epub 2010 Apr 19. Thrombin elicits functional responses critical to blood homeostasis by interacting with diverse physiological substrates. Ala-scanning mutagenesis of 97 residues covering 53% of the solvent accessible surface area of the enzyme identifies Trp(215) as the single most important determinant of […]
View Post autolysis loop, fibrinogen, Protein C, protein C activation, W215APapaconstantinou ME, Bah A, Di Cera E. Cell Mol Life Sci. 2008 Jun;65(12):1943-7. The A chain of thrombin is covalently linked to the catalytic B chain but is separate from any known epitope for substrate recognition. In this study we present the results of the Ala replacement of 12 charged residues controlling the stability of the A chain […]
View Post A Chain, protein C activation, Thrombin, thrombodulinGruber A, Marzec UM, Bush L, Di Cera E, Fernández JA, Berny MA, Tucker EI, McCarty OJ, Griffin JH, Hanson SR. Blood. 2007 May 1;109(9):3733-40. Epub 2007 Jan 16. The anticoagulant and anti-inflammatory enzyme, activated protein C (APC), naturally controls thrombosis without affecting hemostasis. We therefore evaluated whether the integrity of primary hemostasis was preserved […]
View Post Anticoagulant, fibrin formation, protein C activationGruber A, Marzec UM, Bush L, Di Cera E, Fernández JA, Berny MA, Tucker EI, McCarty OJ, Griffin JH, Hanson SR. Blood. 2007 May 1;109(9):3733-40. Epub 2007 Jan 16. The anticoagulant and anti-inflammatory enzyme, activated protein C (APC), naturally controls thrombosis without affecting hemostasis. We therefore evaluated whether the integrity of primary hemostasis was preserved during limited pharmacological antithrombotic protein C activator (PCA) treatment in […]
View Post antithrombotic, double-mutant thrombin, enzyme, Glu217Ala, Protein C, protein C activation, Trp215AlaFeistritzer C, Schuepbach RA, Mosnier LO, Bush LA, Di Cera E, Griffin JH, Riewald M. J Biol Chem. 2006 Jul 21;281(29):20077-84 Activated protein C (APC) has endothelial barrier protective effects that require binding to endothelial protein C receptor (EPCR) and cleavage of protease activated receptor-1 (PAR1) and that may play a role in the anti-inflammatory action of APC. In this study we […]
View Post E217A, protein C activation, W215A, W215A/E217AGruber A, Fernández JA, Bush L, Marzec U, Griffin JH, Hanson SR, DI Cera E. J Thromb Haemost. 2006 Feb;4(2):392-7. Anticoagulation with activated protein C (APC) reduces the mortality of severe sepsis. We investigated whether the circulating protein C (PC) pool could be utilized for sustained anticoagulation by endogenous APC. To generate APC without procoagulant effects, we administered the anticoagulant thrombin mutant […]
View Post Anticoagulation, PC Zymogen, Protein C, protein C activation, W215A, W215A/E217AGruber, Andras; Hanson, Stephen R.; Di Cera, Enrico. US patent 20040120943 A1. Abstract: The present invention relates to novel antithrombotic variants of thrombin or fragments thereof that are capable of proteolytically activating protein C, but which are substantially free of fibrinogen cleavage activity. The present invention further relates to variant polypeptides that may be cleaved […]
View Post antithrombotic, protein C activation, Thrombin