help button home button Biophys. J.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mouawad, L.
Right arrow Articles by Guilbert, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mouawad, L.
Right arrow Articles by Guilbert, C.

Biophys J, June 2002, p. 3224-3245, Vol. 82, No. 6

New Insights into the Allosteric Mechanism of Human Hemoglobin from Molecular Dynamics Simulations

Liliane Mouawad, David Perahia, Charles H. Robert, and Christophe Guilbert

Laboratoire de Modélisation et Ingénierie des Protéines, Institut de Biochimie et de Biophysique Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8619, Université Paris-Sud, 91405 Orsay cedex, France

It is still difficult to obtain a precise structural description of the transition between the deoxy T-state and oxy R-state conformations of human hemoglobin, despite a large number of experimental studies. We used molecular dynamics with the Path Exploration with Distance Constraints (PEDC) method to provide new insights into the allosteric mechanism at the atomic level, by simulating the T-to-R transition. The T-state molecule in the absence of ligands was seen to have a natural propensity for dimer rotation, which nevertheless would be hampered by steric hindrance in the "joint" region. The binding of a ligand to the alpha  subunit would prevent such hindrance due to the coupling between this region and the alpha  proximal histidine, and thus facilitate completion of the dimer rotation. Near the end of this quaternary transition, the "switch" region adopts the R conformation, resulting in a shift of the beta  proximal histidine. This leads to a sliding of the beta -heme, the effect of which is to open the beta -heme's distal side, increasing the accessibility of the Fe atom and thereby the affinity of the protein. Our simulations are globally consistent with the Perutz strereochemical mechanism.

Biophys J, June 2002, p. 3224-3245, Vol. 82, No. 6
© 2002 by the Biophysical Society   0006-3495/02/06/3224/22  $2.00


This article has been cited by other articles:


Home page
 Biophys. JHome page
M. Laberge and T. Yonetani
Molecular Dynamics Simulations of Hemoglobin A in Different States and Bound to DPG: Effector-Linked Perturbation of Tertiary Conformations and HbA Concerted Dynamics
Biophys. J., April 1, 2008; 94(7): 2737 - 2751.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. E. Alcantara, C. Xu, T. G. Spiro, and V. Guallar
A quantum-chemical picture of hemoglobin affinity
PNAS, November 20, 2007; 104(47): 18451 - 18455.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
M. Anselmi, M. Brunori, B. Vallone, and A. Di Nola
Molecular Dynamics Simulation of Deoxy and Carboxy Murine Neuroglobin in Water
Biophys. J., July 15, 2007; 93(2): 434 - 441.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
S. Fernandez-Alberti, D. E. Bacelo, R. C. Binning Jr., J. Echave, M. Chergui, and J. Lopez-Garriga
Sulfide-Binding Hemoglobins: Effects of Mutations on Active-Site Flexibility
Biophys. J., September 1, 2006; 91(5): 1698 - 1709.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
S. Maguid, S. Fernandez-Alberti, L. Ferrelli, and J. Echave
Exploring the Common Dynamics of Homologous Proteins. Application to the Globin Family
Biophys. J., July 1, 2005; 89(1): 3 - 13.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
K. Victor, A. Van-Quynh, and R. G. Bryant
High Frequency Dynamics in Hemoglobin Measured by Magnetic Relaxation Dispersion
Biophys. J., January 1, 2005; 88(1): 443 - 454.
[Abstract] [Full Text] [PDF]

Home page
 Protein Sci.Home page
P. Roche, L. Mouawad, D. Perahia, J.-P. Samama, and D. Kahn
Molecular dynamics of the FixJ receiver domain: movement of the {beta}4-{alpha}4 loop correlates with the in and out flip of Phe101
Protein Sci., November 1, 2002; 11(11): 2622 - 2630.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2002 by the Biophysical Society.