Academic Journal
In-Silico Characterization of von Willebrand Factor Bound to FVIII
| العنوان: | In-Silico Characterization of von Willebrand Factor Bound to FVIII |
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| المؤلفون: | Drago, Valentina, Di Paola, Luisa, Lesieur, Claire, Bernardini, Renato, Bucolo, Claudio, Platania, Chiara Bianca Maria |
| المساهمون: | Università degli studi di Catania = University of Catania (Unict), Università Campus Bio-Medico di Roma / University Campus Bio-Medico of Rome ( UCBM), Ampère, Département Bioingénierie (BioIng), Ampère (AMPERE), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) |
| المصدر: | ISSN: 2076-3417. |
| بيانات النشر: | HAL CCSD Multidisciplinary digital publishing institute (MDPI) |
| سنة النشر: | 2022 |
| المجموعة: | HAL Lyon 1 (University Claude Bernard Lyon 1) |
| مصطلحات موضوعية: | hemophilia A, FVIII, von Willebrand Factor, protein contact networks, bioinformatics, biologic drugs, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] |
| الوصف: | International audience ; Factor VIII belongs to the coagulation cascade and is expressed as a long pre-protein (mature form, 2351 amino acids long). FVIII is deficient or defective in hemophilic A patients, who need to be treated with hemoderivatives or recombinant FVIII substitutes, i.e., biologic drugs. The interaction between FVIII and von Willebrand factor (VWF) influences the pharmacokinetics of FVIII medications. In vivo, full-length FVIII (FL-FVIII) is secreted in a plasma-inactive form, which includes the B domain, which is then proteolyzed by thrombin protease activity, leading to an inactive plasma intermediate. In this work, we analyzed through a computational approach the binding of VWF with two structure models of FVIII (secreted full-length with B domain, and B domain-deleted FVIII). We included in our analysis the atomic model of efanesoctocog alfa, a novel and investigational recombinant FVIII medication, in which the VWF is covalently linked to FVIII. We carried out a structural analysis of VWF/FVIII interfaces by means of protein–protein docking, PISA (Proteins, Interfaces, Structures and Assemblies), and protein contact networks (PCN) analyses. Accordingly, our computational approaches to previously published experimental data demonstrated that the domains A3-C1 of B domain-deleted FVIII (BDD-FVIII) is the preferential binding site for VWF. Overall, our computational approach applied to topological analysis of protein–protein interface can be aimed at the rational design of biologic drugs other than FVIII medications. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | hal-03814955; https://hal.science/hal-03814955; https://hal.science/hal-03814955/document; https://hal.science/hal-03814955/file/applsci-12-07855-v2%281%29.pdf |
| DOI: | 10.3390/app12157855 |
| الاتاحة: | https://hal.science/hal-03814955 https://hal.science/hal-03814955/document https://hal.science/hal-03814955/file/applsci-12-07855-v2%281%29.pdf https://doi.org/10.3390/app12157855 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.9841A6E5 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/app12157855 |
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