Urea primarily works on proteins by altering water structure and dynamics, which facilitates protein unfolding.
Urea is a powerful denaturant for proteins. While it can interact directly with the protein backbone and side chains, one significant mechanism, as highlighted in research, involves its effect on the surrounding water molecules.
Altering Water Structure and Dynamics
Urea disrupts the intricate network of hydrogen bonds between water molecules. This disruption is described as altering water structure and dynamics. Essentially, urea makes water a less effective solvent for nonpolar substances.
Diminishing the Hydrophobic Effect
Proteins typically fold in a way that hides their hydrophobic (water-repelling) amino acid residues in the core, minimizing their contact with water. This phenomenon is known as the hydrophobic effect and is a major driving force for protein folding.
By altering water structure and dynamics, urea behaves similarly to the introduction of nonpolar groups into water. This makes the water less structured and less able to "push" hydrophobic groups together to avoid contact. Consequently, the strength of the hydrophobic effect is significantly diminished.
Facilitating Unfolding and Exposure of Hydrophobic Core
With a weakened hydrophobic effect, the protein's nonpolar core is no longer as strongly driven to remain buried. Urea's presence makes it energetically more favorable for these hydrophobic residues to be exposed to the solvent. This facilitating the exposure of the hydrophobic core residues leads to the unfolding of the protein from its compact, native state into a more extended, denatured state.
In summary, urea's action on proteins is complex, involving both direct interactions and, importantly, an indirect mechanism through its effect on water that weakens the crucial hydrophobic effect, driving protein unfolding.
