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Proposed structural models of the prothrombinase (FXa–FVa) complex
Author(s) -
Autin Ludovic,
Steen Mårten,
Dahlbäck Björn,
Villoutreix Bruno O.
Publication year - 2006
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20848
Subject(s) - docking (animal) , prothrombinase , chemistry , macromolecular docking , thrombin , stereochemistry , protein structure , biochemistry , biology , immunology , medicine , platelet , nursing
Abstract Activated coagulation factor V (FVa) functions as a cofactor to factor Xa (FXa) in the conversion of prothrombin (PT) to thrombin. This essential procoagulant reaction, despite being the subject of extensive investigation, is not fully understood structurally and functionally. To elucidate the structure of the FXa–FVa complex, we have performed protein:protein (Pr:Pr) docking simulation with the pseudo‐Brownian Pr:Pr docking ICM package and with the shape‐complementarity Pr:Pr docking program PPD. The docking runs were carried out using a new model of full‐length human FVa and the X‐ray structure of human FXa. Five representative models of the FXa–FVa complex were in overall agreement with some of the available experimental data, but only one model was found to be consistent with almost all of the reported experimental results. The use of hybrid docking approach (theoretical plus experimental) is definitively important to study such large macromolecular complexes. The FXa–FVa model we have created will be instrumental for further investigation of this macromolecular system and will guide future site directed mutagenesis experiments. Proteins 2006. © 2006 Wiley‐Liss, Inc.