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- W1987360507 endingPage "6779" @default.
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- W1987360507 abstract "Thrombin is a serine protease that acts as a procoagulant by clotting fibrinogen and activating platelets and as an anticoagulant by activating protein C in a thrombomodulin-dependent reaction. Fibrinogen and thrombomodulin bind competitively to an anion-binding exosite on thrombin. We prepared recombinant normal human thrombin and mutant thrombins with single amino acid substitutions in order to localize and distinguish the fibrinogen- and thrombomodulin-binding sites. Normal and mutant thrombins had similar amidolytic activity. Thrombin K52E had approximately 2.5-fold increased protein C-activating activity but only approximately 17% of normal fibrinogen-clotting activity. Thrombin R70E had normal fibrinogen-clotting activity but only approximately 7% of normal protein C-activating activity. Thrombin R68E had markedly reduced activity in both assays. Decreased activation of protein C correlated with decreased binding affinity for thrombomodulin, and ability to activate platelets correlated directly with fibrinogen-clotting activity. These results demonstrate that thrombins with predominantly anticoagulant or procoagulant activity can be created by mutagenesis and that thrombomodulin- and fibrinogen-binding sites on thrombin may overlap but are not identical." @default.
- W1987360507 created "2016-06-24" @default.
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- W1987360507 date "1991-08-01" @default.
- W1987360507 modified "2023-09-30" @default.
- W1987360507 title "Single amino acid substitutions dissociate fibrinogen-clotting and thrombomodulin-binding activities of human thrombin." @default.
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- W1987360507 doi "https://doi.org/10.1073/pnas.88.15.6775" @default.
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