Protein Chemistry - Part 1 - General Protein Chemistry - Ashmarin I. P. 1968

Protein Denaturation

Denaturation is a highly distinctive property of Proteins and represents a complex phenomenon driven by alterations in the secondary, tertiary, and quaternary structures of the protein molecule. It is well established that synthetic and natural Polypeptides do not undergo denaturation. Polymeric CARBOHYDRATES and other high-molecular-weight substances are likewise incapable of denaturing. It follows, therefore, that neither macromolecular nature nor chemical composition alone is sufficient to explain this unique characteristic of proteins. All available evidence indicates that Protein Denaturation is an intramolecular rearrangement that occurs without the Cleavage of peptide bonds, resulting in the loss of the unique spatial arrangement and conformation of The polypeptide chains; as a rule, this is accompanied by the loss of the specific biological activity characteristic of the native protein. Denaturation does not include processes associated with the hydrolytic (proteolytic) cleavage of peptide bonds, nor does it encompass various other reversible and irreversible protein alterations caused by reactions of individual functional groups that do not affect the protein molecule as a whole (such as interactions with numerous ions, the incorporation of specific organic substituents, etc.).

As shown in Chapter V of this manual, the secondary, tertiary, and quaternary structures of a native protein are largely maintained by a system of Hydrogen Bonds and hydrophobic interactions between amino acid residues. The properties of a native protein, particularly its biological activity, depend on a strictly defined, unique spatial arrangement and configuration of its polypeptide chains. Through various external influences, such as heating, it is possible to temporarily disrupt a portion of these hydrogen bonds and weaken hydrophobic interactions. However, if the agent is subsequently removed and conditions are restored to favor The formation of the broken bonds, the original unique Structure is generally not recovered; the newly formed bonds re-establish themselves randomly rather than at the precise locations they occupied in the native protein. As a result, the resulting stable structures differ significantly from the original and, naturally, lack specific biological activity. These are denatured protein molecules. It is understandable that while the native structure is unique, denaturation products can be remarkably diverse. Only for relatively simple proteins consisting of a single polypeptide chain (such as Ribonuclease, Trypsin, etc.) has it proven possible to restore the native conformation and biological activity under specific conditions. Thus, in the majority of cases, denaturation is an irreversible process.

Current concepts holding that denaturation is rooted in conformational changes of protein polypeptide chains align remarkably well with Wu's hypothesis, formulated at a time when biochemists lacked sufficiently precise understanding of secondary and tertiary protein structures and the forces stabilizing them.