Structure and dynamics of zymogen human blood coagulation factor X

Biophys J. 2002 Mar;82(3):1190-206. doi: 10.1016/S0006-3495(02)75476-3.


The solution structure and dynamics of the human coagulation factor X (FX) have been investigated to understand the key structural elements in the zymogenic form that participates in the activation process. The model was constructed based on the 2.3-A-resolution x-ray crystallographic structure of active-site inhibited human FXa (PDB:1XKA). The missing gamma-carboxyglutamic acid (GLA) and part of epidermal growth factor 1 (EGF1) domains of the light chain were modeled based on the template of GLA-EGF1 domains of the tissue factor (TF)-bound FVIIa structure (PDB:1DAN). The activation peptide and other missing segments of FX were introduced using homology modeling. The full calcium-bound model of FX was subjected to 6.2 ns of molecular dynamics simulation in aqueous medium using the AMBER6.0 package. We observed significant reorientation of the serine-protease (SP) domain upon activation leading to a compact multi-domain structure. The solution structure of zymogen appears to be in a well-extended conformation with the distance between the calcium ions in the GLA domain and the catalytic residues estimated to be approximately 95 A in contrast to approximately 83 A in the activated form. The latter is in close agreement with fluorescence studies on FXa. The S1-specificity residues near the catalytic triad show significant differences between the zymogen and activated structures.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Carboxyglutamic Acid / chemistry
  • Amino Acid Sequence
  • Binding Sites
  • Blood Coagulation Factors / chemistry*
  • Catalytic Domain
  • Crystallography, X-Ray
  • Enzyme Precursors / blood*
  • Enzyme Precursors / chemistry*
  • Enzyme Precursors / genetics
  • Epidermal Growth Factor / chemistry
  • Factor X / chemistry*
  • Factor X / genetics
  • Factor Xa / chemistry
  • Humans
  • Hydrogen Bonding
  • Models, Biological
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Protein Conformation
  • Protein Structure, Tertiary
  • Serine Endopeptidases / metabolism


  • Blood Coagulation Factors
  • Enzyme Precursors
  • 1-Carboxyglutamic Acid
  • Epidermal Growth Factor
  • Factor X
  • Serine Endopeptidases
  • Factor Xa

Associated data

  • PDB/1DAN