What is the Origin of Asparagine Deamidation?

This concept is a fundamental principle of protein chemistry, where the intrinsic instability of the asparagine side chain has been characterized since the early studies of protein primary structure and degradation. It describes an unavoidable chemical process inherent to the biological environment, particularly under physiological conditions of temperature and pH. The study of deamidation provides insight into the intrinsic lifespan and stability of cellular components.

What is the Mechanism of Asparagine Deamidation?

The process begins with the nitrogen atom of the adjacent peptide bond attacking the asparagine side chain's carbonyl carbon, forming a highly strained and reactive succinimide intermediate. This intermediate is unstable and rapidly hydrolyzes, typically resulting in a mixture of the normal L-aspartic acid and the structurally aberrant L-isoaspartic acid. The introduction of the isoaspartic acid residue alters the protein's native three-dimensional fold, often leading to a loss of biological activity, increased aggregation, and marking the protein for degradation.

Asparagine Deamidation

Meaning

Asparagine Deamidation is a non-enzymatic post-translational modification in which the amide side chain of an asparagine residue within a protein undergoes hydrolysis, converting it into either aspartic acid or isoaspartic acid. This spontaneous chemical reaction is a major pathway for protein damage and is considered a critical molecular mechanism contributing to cellular aging and protein dysfunction. The integrity of numerous long-lived proteins is compromised by the accumulation of these deamidation events over time.