Abstract | BACKGROUND: OBJECTIVES: The purpose of this study was to establish three-dimensional (3D) models of the FVIIIa-FIXa complex. METHODS: First, we built two new theoretical models of FVIIIa via homology modeling, inter-domain docking and loop simulation algorithms as well as a model for FIXa. This was followed by pseudo-Brownian protein- protein docking in internal coordinates with the ICM (Internal Coordinates Mechanics) program between the two FVIIIa and the FIXa structures. RESULTS: Ten representative models of this complex are presented based on agreements with known experimental data and according to structural criteria. CONCLUSIONS: These novel 3D models will help guide future site directed mutagenesis aimed at improving the functionality of FVIIIa and/or FIXa and will contribute to a better understanding of the role of this macromolecular complex in the blood coagulation cascade.
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Authors | L Autin, M A Miteva, W H Lee, K Mertens, K-P Radtke, B O Villoutreix |
Journal | Journal of thrombosis and haemostasis : JTH
(J Thromb Haemost)
Vol. 3
Issue 9
Pg. 2044-56
(Sep 2005)
ISSN: 1538-7933 [Print] England |
PMID | 16102111
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Multiprotein Complexes
- Neoplasm Proteins
- Factor VIIIa
- Factor IXa
- Cysteine Endopeptidases
- cancer procoagulant
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Topics |
- Algorithms
- Blood Coagulation
- Cysteine Endopeptidases
(chemistry)
- Factor IXa
(chemistry)
- Factor VIIIa
(chemistry)
- Humans
- Models, Molecular
- Multiprotein Complexes
(chemistry)
- Neoplasm Proteins
(chemistry)
- Protein Binding
- Protein Conformation
- Structural Homology, Protein
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