Premium
Thrombin as procoagulant and anticoagulant
Author(s) -
CERA E. DI
Publication year - 2007
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2007.02485.x
Subject(s) - thrombin , serine protease , chemistry , allosteric regulation , coagulation , fibrinogen , biochemistry , protein c , discovery and development of direct thrombin inhibitors , anticoagulant , thrombomodulin , protease , enzyme , pharmacology , biology , medicine , immunology , platelet
Summary. 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.