Thrombosis Research
Volume 125, Supplement 1 , Pages S7-S10, April 2010

Recent Estimates of the Structure of the Factor VIIa (FVIIa)/Tissue Factor (TF) and Factor Xa (FXa) Ternary Complex

  • Chang Jun Lee

      Affiliations

    • Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599-3290, USA
    • ,
  • Vasu Chandrasekaran

      Affiliations

    • Novartis Institutes for Biomedical Research, Cambridge, MA, USA 02139
    • ,
  • Sangwook Wu

      Affiliations

    • Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599-3290, USA
    • ,
  • Robert E. Duke

      Affiliations

    • Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599-3290, USA
    • ,
  • Lee G. Pedersen

      Affiliations

    • Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599-3290, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 919 962 1578; fax: +1 919 962 2388.

published online 22 February 2010.

Abstract 

The putative structure of the Tissue Factor/Factor VIIa/Factor Xa (TF/FVIIa/FXa) ternary complex is reconsidered. Two independently derived docking models proposed in 2003 (one for our laboratory: CHeA and one from the Scripps laboratory: Ss) are dynamically equilibrated for over 10ns in an electrically neutral solution using all-atom molecular dynamics. Although the dynamical models (CHeB and Se) differ in atomic detail, there are similarities in that TF is found to interact with the γ-carboxyglutamic acid (Gla) and Epidermal Growth Factor-like 1 (EGF-1) domains of FXa, and FVIIa is found to interact with the Gla, EGF-2 and serine protease (SP) domains of FXa in both models. FVIIa does not interact with the FXa EGF-1 domain in Se and the EGF domains of FVIIa do not interact with FXa in the CHeB. Both models are consistent with experimentally suggested contacts between the SP domain of FVIIa with the EGF-2 and SP domains of FXa.

Keywords: Factor VIIa, Tissue factor, Factor Xa, ternary complex, Molecular Dynamics simulation

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PII: S0049-3848(10)00075-7

doi:10.1016/j.thromres.2010.01.022

Thrombosis Research
Volume 125, Supplement 1 , Pages S7-S10, April 2010

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