Proposed structural models of human factor Va and prothrombinase.
BACKGROUND
The prothrombinase complex consists of factor Xa, FVa, calcium ions, and phospholipid membrane. The prothrombinase complex plays a key role in the blood coagulation process.


OBJECTIVE
To derive solvent-equilibrated models of human FVa and the prothrombinase complex.


METHODS
Several modeling techniques have been employed, including homology modeling, protein-protein docking, and molecular dynamics simulation methods, to build the structural models.


CONCLUSIONS
We found, upon simulation, a possibly significant shift towards planarity of the five FVa domains. To estimate a prothrombinase structure, we docked an FXa model to the equilibrated FVa model using experimental data as docking filters. We found that simulation of the docked complex led to some changes in the protein-protein contacts, but not buried surface area, as compared to the initial docking model. Possible locations of prothrombin binding to prothrombinase are indicated.
Lee
C J
CJ
Department of Chemistry, UNC-CH, Chapel Hill, NC, USA.
Lin
P
P
Chandrasekaran
V
V
Duke
R E
RE
Everse
S J
SJ
Perera
L
L
Pedersen
L G
LG
D003198:Computer Simulation; D015943:Factor Va / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008961:Models, Structural; D011485:Protein Binding; D011487:Protein Conformation; D012997:Solvents; D013925:Thromboplastin / Q000737:chemistry* / Q000378:metabolism
D012997:Solvents; D015943:Factor Va; D013925:Thromboplastin