title: Transition state analysis of the complex between coagulation factor VIIa and tissue factor: suggesting a sequential domain-binding pathway.
abstract: Injury of a blood vessel exposes membrane-bound tissue factor (TF) to blood, which allows binding of coagulation factor VIIa (FVIIa). This initiation of the coagulation cascade is dictated by a specific multi-domain interaction between FVIIa and TF. To examine the energies involved in the transition state of the FVIIa:TF complex, various residues in the extracellular part of TF (sTF) that are known to interact with FVIIa were replaced with a smaller cysteine residue. Determination of Phi values in each of the positions using surface plasmon resonance measurements enabled us to characterize the transition state complex between the resulting sTF variants and FVIIa. We found that the interactions in the transition state seemed to be most pronounced between the protease domain of FVIIa and sTF while detailed specific interactions between the Gla-domain and sTF were missing. Thus, the transition state energy data indicate a sequential binding event between these two macromolecules.
authors.affiliation: IFM-Department of Chemistry, Linköping University, SE-581 83 Linköping, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Osterlund
authors.forename: Egon
authors.initials: E
authors.lastname: Persson
authors.forename: Magdalena
authors.initials: M
authors.lastname: Svensson
authors.forename: Uno
authors.initials: U
authors.lastname: Carlsson
authors.forename: Per-Ola
authors.initials: PO
authors.lastname: Freskgård
mesh_terms: D001777:Blood Coagulation / Q000502:physiology*; D004735:Energy Transfer; D015942:Factor VIIa / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D017434:Protein Structure, Tertiary / Q000502:physiology; D013816:Thermodynamics; D013925:Thromboplastin / Q000737:chemistry / Q000378:metabolism*; D013997:Time Factors
chemical_list: D013925:Thromboplastin; D015942:Factor VIIa