Title: Counteraction of Urea by Trimethylamine N-Oxide Is Due to Direct Interaction
Authors: Meersman, Filip ×
Bowron, Daniel
Soper, Alan K
Koch, Michel H. J #
Issue Date: Nov-2009
Publisher: Cell press
Series Title: Biophysical journal vol:97 issue:9 pages:2559-2566
Abstract: Trimethylamine N-oxide (TMAO) is a naturally occurring osmolyte that stabilizes proteins, induces folding, and counteracts the denaturing effects of urea, pressure, and ice. To establish the mechanism behind these effects, isotopic substitution neutron-scattering measurements were performed on aqueous solutions of TMAO and 1:1 TMAO-urea at a solute mole fraction of 0.05. The partial pair distribution functions were extracted using the empirical potential structure refinement method. The results were compared with previous results obtained with isosteric tert-butanol, as well as the available data from spectroscopy and molecular-dynamics simulations. In solution, the oxygen atom of TMAO is strongly hydrogen-bonded to, on average, between two and three water molecules, and the hydrogen-bond network is tighter in water than in pure water. In TMAO-urea solutions, the oxygen atom in TMAO preferentially forms hydrogen bonds with urea. This explains why the counteraction is completed at a 2:1 urea/TMAO concentration ratio, independently of urea concentration. These results strongly support models for the effect of TMAO on the stability of proteins based on a modification of the simultaneous equilibria that control hydrogen bonding between the peptide backbone and water or intramolecular sites, without any need for direct interaction between TMAO and the protein.
ISSN: 0006-3495
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Imaging and Photonics
× corresponding author
# (joint) last author

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