Cation-amino acid interactions: Implications for protein destabilization.

The mechanism for protein stabilization or destabilization has long been an open quest. In the present study, we have studied the interactions between amino acids and guanidinium (Gdm)/ammonium (NH) ions by using low field nuclear magnetic resonance (LF-NMR), where Gdm and NH are denaturant and stabilizer for proteins, respectively. It shows that Gdm favors to bind to the thiol group or the hydroxyl group on the side chain but weakly interacts with the α-carboxyl group. In contrast, NH prefers to bind to the α-carboxyl group but slightly interacts with the thiol group or the hydroxyl group on the side chain of amino acids. HNMR reveals the hydrogen bonding between NH and the α-carboxyl group, which is not involved in the interactions between Gdm and cysteine. Our study demonstrates that the strong interactions between the denaturant and the sulfur atom or the disulfide bond promote the direct binding of the denaturant toward proteins, leading to the destabilization.