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Updated: Jun 30, 2026
13:08
Measurement of Factor V Activity in Human Plasma Using a Microplate Coagulation Assay
Published on: September 9, 2012
Predicted solution structure of zymogen human coagulation FVII
Lalith Perera1, Thomas A Darden, Lee G Pedersen
1Department of Chemistry, University of North Carolina, Chapel Hill 27599-3290, USA.
Journal of Computational Chemistry
|March 27, 2002
Summary
This study models the human zymogen FVII structure without tissue factor (TF), revealing significant interdomain motions. The zymogen FVII structure is similar to TF-bound forms, with minimal protease domain changes upon activation.
Area of Science:
- Biochemistry
- Structural Biology
- Computational Biology
Background:
- Human coagulation Factor VII (FVII) is a key initiator of the extrinsic pathway.
- Understanding FVII's conformational states is crucial for studying its activation and tissue factor (TF) binding.
Purpose of the Study:
- To construct a model solution structure of calcium ion-bound human zymogen FVII in the absence of TF.
- To investigate conformational changes during FVII activation and TF binding.
Main Methods:
- Molecular dynamics simulations using the Amber force field and PME electrostatics.
- Comparison of the modeled solution structure with existing X-ray crystallographic data of FVIIa.
Main Results:
- The zymogen FVII solution structure is predicted to be extended, similar to TF-bound FVIIa.
- Significant interdomain motions were observed between Gla-EGF1 and EGF1-EGF2 domains.
- Minimal restructuring of the serine protease domain occurred upon simulated activation.
Conclusions:
- The zymogen FVII structure exhibits flexibility, particularly in interdomain regions.
- TF binding and activation induce subtle rather than drastic structural rearrangements in the protease domain.
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