Deamidation

Deamidation is the reverse reaction of amidation and involves release of an amine from an amide. Deamidation occurs spontaneously in proteins at asparagine and glutamine residues, which causes heterogeneity, instability, and sometimes defects in the function of the proteins.

 Deamidation in proteins occurs enzymatically or chemically. Enzymes that participate in deamidating of proteins are transglutaminase and peptidoglutaminase. An amide bond in an asparagine or glutamine residue is relatively labile, especially in acidic media, and is easily hydrolyzed chemically. The rate of deamidation is sensitive to the environment of the amide. Exposed amides are more readily deamidated than those buried in the interior of a protein. Thus, denatured proteins often have high potential for deamidation.

The Asn-Gly sequence is especially notorious for rapid deamidation. The reaction shown below proceeds readily in this sequence. Additional reactions such as racemization, transpeptidation, and cleavage of peptide bonds take place during this reaction. These reactions also occur with the Asp-Gly sequence and pivotal components of protein deterioration.

The rates of deamidation vary with different peptides. The half-times for deamidation of various asparagine residues under the same conditions range from 3.3 to 277 days. Deamidation causes conformational destabilization of proteins and accelerates their degradation. Thus the deamidation of Asn or Gln residues has been regarded as a timer of protein turnover (1).

Asparaginase hydrolyzes asparagine to aspartic acid (deamidation). Because asparagine in the blood is an essential nutrient for the growth of malignant white cells, the intravenous administration of asparaginase suppresses the growth of some types of animal and human leukemias.

References

1. A.B. Robinson, J.H. McKerrow, and P. Cary (1970) Proc. Natl. Acad. Sci. USA 665, 753–757.