| http://purl.uniprot.org/citations/35551912 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35551912 | http://www.w3.org/2000/01/rdf-schema#comment | "Protein Z (PZ)-dependent protease inhibitor (ZPI) is a plasma anticoagulant protein of the serpin superfamily, which is activated by its cofactor, PZ, to rapidly inhibit activated factor X (FXa) on a procoagulant membrane surface. ZPI is also activated by heparin to inhibit free FXa at a physiologically significant rate. Here, we show that heparin binding to ZPI antagonizes PZ binding to and activation of ZPI. Virtual docking of heparin to ZPI showed that a heparin-binding site near helix H close to the PZ-binding site as well as a previously mapped site in helix C was both favored. Alanine scanning mutagenesis of the helix H and helix C sites demonstrated that both sites were critical for heparin activation. The binding of heparin chains 72 to 5-saccharides in length to ZPI was similarly effective in antagonizing PZ binding and in inducing tryptophan fluorescence changes in ZPI. Heparin binding to variant ZPIs with either the helix C sites or the helix H sites mutated showed that heparin interaction with the higher affinity helix C site most distant from the PZ-binding site was sufficient to induce these tryptophan fluorescence changes. Together, these findings suggest that heparin binding to a site on ZPI extending from helix C to helix H promotes ZPI inhibition of FXa and allosterically antagonizes PZ binding to ZPI through long-range conformational changes. Heparin antagonism of PZ binding to ZPI may serve to spare limiting PZ and allow PZ and heparin cofactors to target FXa at different sites of action."xsd:string |
| http://purl.uniprot.org/citations/35551912 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jbc.2022.102022"xsd:string |
| http://purl.uniprot.org/citations/35551912 | http://purl.uniprot.org/core/author | "Huang X."xsd:string |
| http://purl.uniprot.org/citations/35551912 | http://purl.uniprot.org/core/author | "Swanson R."xsd:string |
| http://purl.uniprot.org/citations/35551912 | http://purl.uniprot.org/core/author | "Olson S.T."xsd:string |
| http://purl.uniprot.org/citations/35551912 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/35551912 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/35551912 | http://purl.uniprot.org/core/pages | "102022"xsd:string |
| http://purl.uniprot.org/citations/35551912 | http://purl.uniprot.org/core/title | "Heparin activation of protein Z-dependent protease inhibitor (ZPI) allosterically blocks protein Z activation through an extended heparin-binding site."xsd:string |
| http://purl.uniprot.org/citations/35551912 | http://purl.uniprot.org/core/volume | "298"xsd:string |
| http://purl.uniprot.org/citations/35551912 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/35551912 |
| http://purl.uniprot.org/citations/35551912 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/35551912 |
| http://purl.uniprot.org/uniprot/#_B2RBZ5-mappedCitation-35551912 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35551912 |
| http://purl.uniprot.org/uniprot/#_G3V2W1-mappedCitation-35551912 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35551912 |
| http://purl.uniprot.org/uniprot/#_Q9UK55-mappedCitation-35551912 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35551912 |
| http://purl.uniprot.org/uniprot/G3V2W1 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/35551912 |
| http://purl.uniprot.org/uniprot/Q9UK55 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/35551912 |
| http://purl.uniprot.org/uniprot/B2RBZ5 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/35551912 |