Philippe Roche§, Liliane Mouawad, David Perahia, Jean-Pierre Samama
and Daniel Kahn
§Division
of Structural Biology, University of Oxford, Henry Wellcome Building for
Genomic Medicine, Roosevelt Drive, Oxford, OX3 7BN, UK.
FixJ is a two domain response regulator involved in nitrogen fixation in
Sinorhizobium meliloti. Recent X-ray
characterization of both the native (unphosphorylated) and the active
(phosphorylated) states of the protein identify conformational changes of the b4-a4 loop and the conserved
residue Phe101 as the key switches in activation[1]1,2. These structures also allowed investigation
of the transition between conformations of this two-component regulatory
receiver domain by molecular dynamics simulations. The path for the conformational
change was studied with a distance constraint directing the system from one
state to the other (“Path Exploration with Distance Constraints” procedure 3).
The simulations provide evidence for a correlation between the conformation of
the b4-a4
loop and the orientation of the conserved residue Phe101 (*). From these simulations, a model presenting the sequence of events
during the activation/deactivation process was proposed 4.
[1]1.- Birck, C., Mourey, L., Gouet, P., Fabry, B.,
Schumacher, J., Rousseau, P., Kahn, D., and Samama, J.P. 1999. Conformational
changes induced by phosphorylation of the FixJ receiver domain. Structure Fold Des. 7: 1505-1515.
2.- Gouet, P., Fabry, B., Guillet, V., Birck,
C., Mourey, L., Kahn, D., and Samama, J.P. 1999. Structural transitions in the
FixJ receiver domain. Structure Fold Des. 7: 1517-1526.
3.- Guilbert, C., Perahia, D., and Mouawad, L.
1995. A method to explore transition paths in macromolecules. Applications to
hemoglobin and phosphoglycerate kinase. Computer
Phys. Comm. 91: 263-274.
4.- Roche, P., Mouawad, L., Perahia, D., Samama, J.P. and Kahn D. 2002.
Molecular dynamics of the FixJ receiver domain: Movement of the b4-a4 loop correlates with the in and out flip of Phe101. Protein Sci. 11: 2622-2630.
(*) Movie presentations of representative
trajectories can be found at the URL
http://www.toulouse.inra.fr/lbmrpm/dk/Fixj_index.html
.