A model for the unique role of factor Va A2 domain extension in the human ternary thrombin-generating complex.
An all-atom human ternary model for the prothrombinase-prothrombin complex, including metal ions and post-translationally modified residues, was constructed from existing X-ray crystal structures. The factor Xa-prothrombin interface was taken from an existing ternary model, which locates the active site of factor Xa in the vicinity of prothrombin cleavage positions. The three sulfotyrosine residues at the C-terminal sequence of factor Va A2 domain are accommodated by modelling rational interactions with positively charged patches on the surface of prothrombin. The entire model is then solvent-equilibrated with molecular dynamics. This ternary model for the thrombin-generating complex provides an estimate as to the role of the C-terminus of the factor Va A2 domain: to establish an interface between FXa and prothrombin and to stabilize the orientation of this interface.
Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA.
Joong-Youn
JY
Shim
Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA.
Chang Jun
CJ
Lee
Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA.
Sangwook
S
Wu
Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA. Electronic address: lee_pedersen@unc.edu.
Lee G
LG
Pedersen
D015943:Factor Va / Q000737:chemistry*; D006801:Humans; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D013917:Thrombin / Q000737:chemistry*
D046912:Multiprotein Complexes; D015943:Factor Va; D013917:Thrombin
coagulation cascade; factor Va A2 domain; prothrombinase; sulfotyrosine; thrombin