ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2009
Plasma protein S contains zinc essential for efficient activated protein C-independent anticoagulant activity and binding to factor Xa, but not for efficient binding to tissue factor pathway inhibitor.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Relationship between serum zinc level and sepsis-induced coagulopathy.International journal of hematology · 2022Article
- Anticoagulant Protein S Targets the Factor IXa Heparin-Binding Exosite to Prevent Thrombosis.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Protein S is a cofactor for platelet and endothelial tissue factor pathway inhibitor-α but not for cell surface-associated tissue factor pathway inhibitor.Arteriosclerosis, thrombosis, and vascular biology · 2014Article
- Zn2+ mediates high affinity binding of heparin to the αC domain of fibrinogen.The Journal of biological chemistry · 2013Article
- Plasma protein S residues 37-50 mediate its binding to factor Va and inhibition of blood coagulation.Thrombosis and haemostasis · 2013Article
- Phosphorylation of protein S by platelet kinases enhances its activated protein C cofactor activity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- Platelet protein S directly inhibits procoagulant activity on platelets and microparticles.Thrombosis and haemostasis · 2013Article
- Protein C anticoagulant and cytoprotective pathways.International journal of hematology · 2012Review
- Antithrombotic activity of protein S infused without activated protein C in a baboon thrombosis model.Thrombosis and haemostasis · 2012Article
- Tissue factor pathway inhibitor: structure-function.Frontiers in bioscience (Landmark edition) · 2012Review
- Haemostatic system in inflammatory bowel diseases: new players in gut inflammation.World journal of gastroenterology · 2011Review
- Zn²(+) -containing protein S inhibits extrinsic factor X-activating complex independently of tissue factor pathway inhibitor.Journal of thrombosis and haemostasis : JTH · 2010Article
- Zinc modulates the interaction of protein C and activated protein C with endothelial cell protein C receptor.The Journal of biological chemistry · 2010Article
- Bisaryl hydrazones as exchangeable biocompatible linkers.Angewandte Chemie (International ed. in English) · 2010Article
- Species-specific anticoagulant and mitogenic activities of murine protein S.Haematologica · 2009Article
- Lack of protein S in mice causes embryonic lethal coagulopathy and vascular dysgenesis.The Journal of clinical investigation · 2009Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Protein S (PS) is a cofactor for activated protein C (APC), which inactivates coagulation factors (F) Va and VIIIa. Deficiency of protein C or PS is associated with risk of thrombosis. We found that PS also has APC-independent anticoagulant activity (PS-direct) and directly inhibits thrombin generated by FXa/FVa (prothrombinase complex). Here we report that PS contains Zn(2+) that is required for PS-direct and that is lost during certain purification procedures. Immunoaffinity-purified PS contained 1.4 +/- 0.6 Zn(2+)/mol, whereas MonoQ-purified and commercial PS contained 0.15 +/- 0.15 Zn(2+)/mol. This may explain the controversy regarding the validity of PS-direct. Zn(2+) content correlated positively with PS-direct in prothrombinase assays and clotting assays, but APC-cofactor activity of PS was independent of Zn(2+) content. PS-direct and Zn(2+) were restored to inactive PS under mildly denaturing conditions. Conversely, o-phenanthroline reversibly impaired the PS-direct of active PS. Zn(2+)-containing PS bound FXa more efficiently (K(d)(app)=9.3 nM) than Zn(2+)-deficient PS (K(d)(app)=110 nM). PS bound TFPI efficiently, independently of Zn(2+) content (K(d)(app)=21 nM). Antibodies that block PS-direct preferentially recognized Zn(2+)-containing PS, suggesting conformation differences at or near the interface of 2 laminin G-like domains near the PS C terminus. Thus, Zn(2+) is required for PS-direct and efficient FXa binding and may play a role in stabilizing PS conformation.
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Registered trials
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