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 Printable version |
Human factor VII activation: mechanisms and perspectives |
Hématologie. Volume 9, Number 2, 125-31, Mars 2003, REVUE
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 Résumé
Article gratuit
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Author(s) : Muriel Giansily‐Blaizot, Shu‐Wen W. Chen, Jean‐François Schved, Jean‐Luc Pellequer |
Summary : Activated factor VII (F VIIa) bound to its membrane cofactor tissue factor (TF) triggers the coagulation cascade. TF is essential for the proteolytic activity of FVIIa and is supposed to allosterically regulate F VIIa. The mechanism in which TF completes the zymogen to enzyme transition is still unclear. The recent determination of a F VII zymogen X‐ray structure, when compared to the F T\\F VIIa X‐ray structure, reveals an important conformational change in the catalytic domain inside the β‐strand B2, modifying adjacent TF binding regions. Therefore, it is tempting to speculate about the existence of an equilibrium between incompetent and competent TF binding conformations for both F VII and free F VIIa, mediated through the registration in the β‐strand B2. This hypothesis would offer interesting physiological and therapeutic perspectives. However, this mechanism for changing the B2 registrations and its two‐state equilibrium remains to be defined. |
Keywords : hemostasis, factor VII, tissue factor, crystallographic structure, mutation |
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