Engineering a protein Z‐dependent protease inhibitor ( ZPI ) mutant as a novel antagonist of ZPI anticoagulant function for hemophilia treatment
نویسندگان
چکیده
منابع مشابه
Structural basis for catalytic activation of protein Z-dependent protease inhibitor (ZPI) by protein Z.
The anticoagulant serpin, protein Z-dependent protease inhibitor (ZPI), is catalytically activated by its cofactor, protein Z (PZ), to regulate the function of blood coagulation factor Xa on membrane surfaces. The X-ray structure of the ZPI-PZ complex has shown that PZ binds to a unique site on ZPI centered on helix G. In the present study, we show by Ala-scanning mutagenesis of the ZPI-binding...
متن کاملPolymorphisms of the protein Z-dependent protease inhibitor (ZPI) gene and the risk of venous thromboembolism.
Thromb Haemost 2006; 95: 909–10 Dear Sir, Protein Z-dependent protease inhibitor (ZPI), together with its cofactor protein Z (PZ), inhibits activated factor Xa (Xa) (1–3). Studies in mice showed that the PZ null genotype increases the mortality in utero of homozygous factor V Leiden mice due to vascular thrombosis and hepatic fibrin deposition (4), suggesting a role for the PZ-ZPI pathway in th...
متن کاملTHROMBOSIS AND HEMOSTASIS Structural basis for catalytic activation of protein Z–dependent protease inhibitor (ZPI) by protein Z
The anticoagulant serpin, protein Z-dependent protease inhibitor (ZPI), is catalytically activated by its cofactor, protein Z (PZ), to regulate the function of blood coagulation factor Xa on membrane surfaces. The X-ray structure of the ZPI-PZ complex has shown that PZ binds to a unique site on ZPI centered on helix G. In the present study, we show by Ala-scanning mutagenesis of the ZPIbinding ...
متن کاملProtein Z and protein Z-dependent protease inhibitor. Determinants of levels and risk of venous thrombosis.
To assess the potential roles of protein Z (PZ) and protein Z-dependent protease inhibitor (ZPI) in venous thrombosis, their plasma levels were measured in 426 individuals with venous thrombosis and 471 control individuals participating in the Leiden Thrombophilia Study. A relationship between the level of PZ or ZPI and venous thrombosis was not detected in the overall case-control study. PZ an...
متن کاملIdentification of factor Xa residues critical for interaction with protein Z-dependent protease inhibitor: both active site and exosite interactions are required for inhibition.
Protein Z-dependent protease inhibitor (ZPI) is a plasma serpin, which can rapidly inactivate factor Xa (fXa) in the presence of protein Z (PZ), negatively charged phospholipids, and Ca2+. To investigate the mechanism by which ZPI inactivates fXa, we expressed the serpin in mammalian cells and characterized its reactivity with both wild-type and selected mutants of fXa that 1) contained substit...
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ژورنال
عنوان ژورنال: Journal of Thrombosis and Haemostasis
سال: 2019
ISSN: 1538-7933,1538-7836
DOI: 10.1111/jth.14610