Characterization of Protein Z-Dependent Protease Inhibitor/Antithrombin Chimeras Provides Insight into the Serpin Specificity of Coagulation Proteases.

ABSTRACT: Protein Z (PZ)-dependent protease inhibitor (ZPI) and antithrombin (AT) are two physiological serpin inhibitors involved in the regulation of proteolytic activities of the blood coagulation cascade. ZPI has restricted protease specificity capable of inhibiting factors Xa (FXa) and XIa (FXIa) but exhibiting no reactivity with other coagulation proteases. Unlike ZPI, AT is a general inhibitor of all coagulation proteases and the only physiological inhibitor of factor IXa (FIXa). To understand the molecular determinants of protease specificity of the two serpins, we engineered two ZPI mutants in which the P12-P3' residues of the reactive center loop of ZPI were replaced with either P12-P3' or P12-P7' residues of AT (ZPI-AT^P12-P3' and ZPI-AT^P12-P7'). The reactivity of chi

SUBMITTER: Yang L 

PROVIDER: S-EPMC5537704 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature