Selective loss of fibrinogen clotting in a loop-less thrombin

The autolysis loop of thrombin comprises nine residues, from Glu(146) to Lys(149e), five of which (Ala(149a)-Lys(149e)) are inserted relative to trypsin and chymotrypsin. Deletion of the insertion Ala(149a)-Lys(149e) causes no significant change in the properties of the enzyme, except for a slight enhancement of protein C activation. Deletion of the entire Glu(146)-Lys(149e) loop, however, reduces fibrinogen clotting 240-fold, but decreases protein C activation only 2-fold. This loop-less mutant is de facto an exclusive activator of protein C, having lost the primary procoagulant function of thrombin. Because the autolysis loop affects fibrinogen binding, but not protein C activation, it provides a target for new drugs designed to suppress exclusively the procoagulant activity of thrombin.