ArticleProceedings of the National Academy of Sciences of the United States of America2001
Rational design of coagulation factor VIIa variants with substantially increased intrinsic activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 117 citations in OpenAlex.
- Recombinant factor VIIa analog in the management of hemophilia with inhibitors: results from a multicenter, randomized, controlled trial of vatreptacog alfa.Journal of thrombosis and haemostasis : JTH · 2014Trial
- Immunopeptidomics of blood coagulation factor IX: a core peptide derived from the protease domain is promiscuously presented on HLA-DR.Research and practice in thrombosis and haemostasis · 2026Article
- Recombinant factor VIIa: new insights into the mechanism of action through product innovation.Research and practice in thrombosis and haemostasis · 2025Review
- A bispecific antibody approach for the potential prophylactic treatment of inherited bleeding disorders.Nature cardiovascular research · 2024Article
- The MHC Associated Peptide Proteomics assay is a useful tool for the non-clinical assessment of immunogenicity.Frontiers in immunology · 2023Article
- Uncovering Membrane-Bound Models of Coagulation Factors by Combined Experimental and Computational Approaches.Thrombosis and haemostasis · 2021Review
- Article
- Beating tissue factor at its own game: Design and properties of a soluble tissue factor-independent coagulation factor VIIa.The Journal of biological chemistry · 2020Article
- Limited factor VIIa surface localization requirement of the factor VIIa-induced overall thrombin generation in platelet-rich hemophilia A plasma.Research and practice in thrombosis and haemostasis · 2019Article
- Mitigation of T-cell dependent immunogenicity by reengineering factor VIIa analogue.Blood advances · 2019Article
- Crystal structure, epitope, and functional impact of an antibody against a superactive FVIIa provide insights into allosteric mechanism.Research and practice in thrombosis and haemostasis · 2019Article
- Protein-Engineered Coagulation Factors for Hemophilia Gene Therapy.Molecular therapy. Methods & clinical development · 2019Review
- Human platelets express endothelial protein C receptor, which can be utilized to enhance localization of factor VIIa activity.Journal of thrombosis and haemostasis : JTH · 2018Article
- Molecular Characterization of Iranian Patients with Inherited Coagulation Factor VII Deficiency.Balkan journal of medical genetics : BJMG · 2017Article
- Recombinant human factor VIIa (rFVIIa) in hemophilia: mode of action and evidence to date.Therapeutic advances in hematology · 2017Review
- Engineering of a membrane-triggered activity switch in coagulation factor VIIa.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Phage-assisted continuous evolution of proteases with altered substrate specificity.Nature communications · 2017Article
- Non-canonical proteolytic activation of human prothrombin by subtilisin fromThe Journal of biological chemistry · 2017Article
- Molecular Basis of Enhanced Activity in Factor VIIa-Trypsin Variants Conveys Insights into Tissue Factor-mediated Allosteric Regulation of Factor VIIa Activity.The Journal of biological chemistry · 2016Article
- Structure-Function Relationship of the Interaction between Tissue Factor and Factor VIIa.Seminars in thrombosis and hemostasis · 2015Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A trace amount of coagulation factor VII (FVII) circulates in the blood in the activated form, FVIIa (EC 3.4.21.21), formed by internal proteolysis. To avoid disseminated thrombus formation, FVIIa remains in a conformation with zymogen-like properties. Association with tissue factor (TF), locally exposed upon vascular injury, is necessary to render FVIIa biologically active and initiate blood clotting. We have designed potent mutants of FVIIa by replacing residues believed to function as determinants for the inherent zymogenicity. The TF-independent rate of factor X activation was dramatically improved, up to about 100-fold faster than that obtained with the wild-type enzyme and close to that of the FVIIa-soluble TF complex. The mutants appear to retain the substrate specificity of the parent enzyme and can be further stimulated by TF. Insights into the mechanism behind the increased activity of the mutants, presumably also pertinent to the TF-induced, allosteric stimulation of FVIIa activity, were obtained by studying their calcium dependence and the accessibility of the N terminus of the protease domain to chemical modification. The FVIIa analogues promise to offer a more efficacious treatment of bleeding episodes especially in hemophiliacs with inhibitory antibodies precluding conventional replacement therapy.
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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.