title: Prothrombin structure: unanticipated features and opportunities.
abstract: The structure of prothrombin has eluded investigators for decades but recent efforts have succeeded in revealing the architecture of this important clotting factor. Unanticipated features have emerged outlining the significant flexibility of the zymogen due to linker regions connecting the γ carboxyglutamic domain, kringles and protease domain. A new, structure-based framework helps in defining a molecular mechanism of prothrombin activation, rationalizes the severe bleeding phenotypes of several naturally occurring mutations and identifies targets for drug design.
authors.affiliation: Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
authors.forename: Nicola
authors.initials: N
authors.lastname: Pozzi
authors.forename: Enrico
authors.initials: E
authors.lastname: Di Cera
mesh_terms: D006801:Humans; D009154:Mutation; D017434:Protein Structure, Tertiary; D011516:Prothrombin / Q000737:chemistry* / Q000235:genetics
chemical_list: D011516:Prothrombin
keywords: blood coagulation; drug design; protease; prothrombin; structural biology