ArticleBlood2012
Structural basis for catalytic activation of protein Z-dependent protease inhibitor (ZPI) by protein Z.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 25 citations in OpenAlex.
- Human Protein Z as the Second Known Heme-Binding Protein from the Endogenous Blood Coagulation Inhibitor System.Chembiochem : a European journal of chemical biology · 2026Article
- Tapping Into the Natural PZ-Independent Anticoagulant Function of ZPI to Inhibit Thrombosis With Minimal Effect on Hemostasis.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- DNA accelerates the protease inhibition of a bacterial serpin chloropin.Frontiers in molecular biosciences · 2023Article
- Heparin activation of protein Z-dependent protease inhibitor (ZPI) allosterically blocks protein Z activation through an extended heparin-binding site.The Journal of biological chemistry · 2022Article
- Low Protein Z Level: A Thrombophilic Risk Biomarker for Acute Coronary Syndrome.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2019Article
- Suppressing protein Z-dependent inhibition of factor Xa improves coagulation in hemophilia A.Journal of thrombosis and haemostasis : JTH · 2019Article
- Lipid oxidation inactivates the anticoagulant function of protein Z-dependent protease inhibitor (ZPI).The Journal of biological chemistry · 2017Article
- Serum amyloid A, protein Z, and C4b-binding protein β chain as new potential biomarkers for pulmonary tuberculosis.PloS one · 2017Article
- Inhibitory serpins. New insights into their folding, polymerization, regulation and clearance.The Biochemical journal · 2016Review
- Thermodynamic and kinetic characterization of the protein Z-dependent protease inhibitor (ZPI)-protein Z interaction reveals an unexpected role for ZPI Lys-239.The Journal of biological chemistry · 2015Article
- Characterization of the protein Z-dependent protease inhibitor interactive-sites of protein Z.Biochimica et biophysica acta · 2014Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
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 interface, together with native PAGE and kinetic analyses of PZ binding to ZPI, that Tyr240 and Asp293 of ZPI are crucial hot spots for PZ binding. Complementary studies with protein Z-protein C chimeras show the importance of both pseudocatalytic and EGF2 domains of PZ for the critical ZPI interactions. To understand how PZ acts catalytically, we analyzed the interaction of reactive loop-cleaved ZPI (cZPI) with PZ and determined the cZPI X-ray structure. The cZPI structure revealed changes in helices A and G of the PZ-binding site relative to native ZPI that rationalized an observed 6-fold loss in PZ affinity and PZ catalytic action. These findings identify the key determinants of catalytic activation of ZPI by PZ and suggest novel strategies for ameliorating hemophilic states through drugs that disrupt the ZPI-PZ interaction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.