Thrombin as procoagulant and anticoagulant

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Abstract

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 feature of thrombin has fostered the rational engineering of mutants with selectively compromised fibrinogen and PAR1 cleavage. The discovery of the Na+ effect on thrombin interaction with substrates and the mapping of functional epitopes by Ala scanning mutagenesis have provided a rational and effective strategy for dissociating the procoagulant and anticoagulant activities of the enzyme. Thrombin mutants with selectively compromised activity toward fibrinogen and PAR1 are effective in vivo as anticoagulant and antithrombotic agents. © 2007 International Society on Thrombosis and Haemostasis.

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APA

Di Cera, E. (2007, July). Thrombin as procoagulant and anticoagulant. Journal of Thrombosis and Haemostasis. https://doi.org/10.1111/j.1538-7836.2007.02485.x

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