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Prog Mol Biol Transl Sci. 2011;99:51-103. doi: 10.1016/B978-0-12-385504-6.00002-6.

Complex assemblies of factors IX and X regulate the initiation, maintenance, and shutdown of blood coagulation.

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1
Department of Molecular Biology, University of Salzburg, Salzburg, Austria.

Abstract

Blood hemostasis is accomplished by a complex network of (anti-)coagulatory and fibrinolytic processes. These physiological processes are implemented by the assembly of multiprotein complexes involving both humoral and cellular components. Coagulation factor X, and particularly, factor IX, exemplify the dramatic enhancement that is obtained by the synergistic interaction of cell surface, inorganic and protein cofactors, protease, and substrate. With a focus on structure-function relationship, we review the current knowledge of activity modulation principles in the coagulation proteases factors IX and X and indicate future challenges for hemostasis research. This chapter is organized by describing the principles of hierarchical activation of blood coagulation proteases, including endogenous and exogenous protease activators, cofactor binding, substrate specificities, and protein inhibitors. We conclude by outlining pharmaceutical opportunities for unmet needs in hemophilia and thrombosis.

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