The Transferable Tail: Fusion of the N-Terminal Acidic Extension of Heparin Cofactor II to α1-Proteinase Inhibitor M358R Specifically Increases the Rate of Thrombin Inhibition †

The conversion of the reactive center bond of the serpin alpha1-proteinase inhibitor (alpha1-PI, also known as alpha1-antitrypsin) from Met-Ser to Arg-Ser decreases the rate at which it inhibits neutrophil elastase and endows it with the ability to inhibit thrombin and activated protein C (APC). Another serpin, heparin cofactor II (HCII), contains a unique N-terminal extension that binds thrombin exosite 1. We fused residues 1-75 of HCII to the …