Denaturation of Proteins

Denaturation is the loss of a protein's natural, biologically active three-dimensional shape -- and, along with it, the loss of the protein's normal biological activity -- brought about by physical or chemical agents that disrupt the folded structure of the polypeptide chain.

A number of common agents and conditions can cause denaturation. Heat is the most familiar: raising the temperature increases molecular motion enough to disrupt the weak interactions holding the folded shape together. Extremes of pH, whether strongly acidic or strongly alkaline, alter the ionisation state of acidic and basic side chains along the chain, disturbing the pattern of attraction that stabilises the folded structure. Heavy-metal ions, such as $\text{Hg}^{2+}$ or $\text{Pb}^{2+}$, can bind to specific groups on the protein and distort its shape. Vigorous mechanical agitation, certain organic solvents, and exposure to ultraviolet radiation can each have a similar disruptive effect.

Crucially, denaturation disturbs only the protein's higher-order folded conformation -- it does not break the covalent peptide bonds that make up the protein's primary structure. The amino-acid sequence itself remains completely intact; what is destroyed is the specific three-dimensional shape into which that sequence had folded. Because a protein's biological activity (its ability to act as an enzyme, a structural material, a transport molecule, and so on) depends entirely on having the correct three-dimensional shape, denaturation almost always results in a complete or substantial loss of biological activity, even though every peptide bond, and every amino acid, is still present and unchanged. …