Question

How urea and guanidine denature proteins, comment on the mechanism.

Answer 1

Mechanism of Urea to denature proteins:

Urea denature proteins in two ways i.e. either directly or indirectly. In the case of direct denaturation, urea hydrogen bonds interacts with polarized/charged peptide groups. This direct interaction intermolecular bonds between the amino acids weakening the overall secondary and tertiary structure of protein. Upon unfolding the urea and water gets the access of the core of protein hence making the denaturation process fast. In the case of indirect interaction, the urea affects the solvents of the solution in which the protein is immersed. By making the changes in the structure and hydrodynamics of the solvent, urea encourages the solvent in destablizing the internal bonds of the protein and then accessing the protein for further denaturation.

Mechanism of Guanidine to denature proteins:

Guanidine destablizes and disrupts the alpha helix by breaking the hydrogen bonding network between water molecules adjacent to the protein. and results in disordering of the protein structure. It increases the entropy of the system by interfering with the intermolecular interactions mediated by non covalent forces such as hydrogen bonds, van der waals forces and hydrophobic interactions which are involved in maintaining the structure of a protein.