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dc.contributor.authorAbdel-Azeim, Safwat
dc.contributor.authorOliva, Romina M.
dc.contributor.authorChermak, Edrisse
dc.contributor.authorDe Cristofaro, Raimondo
dc.contributor.authorCavallo, Luigi
dc.date.accessioned2015-08-03T12:16:54Z
dc.date.available2015-08-03T12:16:54Z
dc.date.issued2014-10-24
dc.identifier.issn00062960
dc.identifier.pmid25313940
dc.identifier.doi10.1021/bi500770p
dc.identifier.urihttp://hdl.handle.net/10754/563850
dc.description.abstractFactor X (FX) is one of the major players in the blood coagulation cascade. Upon activation to FXa, it converts prothrombin to thrombin, which in turn converts fibrinogen into fibrin (blood clots). FXa deficiency causes hemostasis defects, such as intracranial bleeding, hemathrosis, and gastrointestinal blood loss. Herein, we have analyzed a pool of pathogenic mutations, located in the FXa catalytic domain and directly associated with defects in enzyme catalytic activity. Using chymotrypsinogen numbering, they correspond to D102N, T135M, V160A, G184S, and G197D. Molecular dynamics simulations were performed for 1.68 μs on the wild-type and mutated forms of FXa. Overall, our analysis shows that four of the five mutants considered, D102N, T135M, V160A, and G184S, have rigidities higher than those of the wild type, in terms of both overall protein motion and, specifically, subpocket S4 flexibility, while S1 is rather insensitive to the mutation. This acquired rigidity can clearly impact the substrate recognition of the mutants.
dc.description.sponsorshipResearch reported in this publication was supported by the King Abdullah University of Science and Technology.
dc.publisherAmerican Chemical Society (ACS)
dc.titleMolecular dynamics characterization of five pathogenic factor X mutants associated with decreased catalytic activity
dc.typeArticle
dc.contributor.departmentChemical Science Program
dc.contributor.departmentKAUST Catalysis Center (KCC)
dc.contributor.departmentPhysical Science and Engineering (PSE) Division
dc.identifier.journalBiochemistry
dc.contributor.institutionDepartment of Sciences and Technologies, University Parthenope of Naples, Centro Direzionale Isola C4Naples, Italy
dc.contributor.institutionHemostasis Research Centre, Institute of Internal Medicine and Geriatrics, Catholic University School of MedicineRome, Italy
dc.contributor.institutionDipartimento di Chimica e Biologia, University of Salerno, Via Papa Giovanni Paolo IIFisciano, Italy
kaust.personAbdel-Azeim, Safwat
kaust.personChermak, Edrisse
kaust.personCavallo, Luigi
dc.date.published-online2014-10-24
dc.date.published-print2014-11-11


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