Isoaspartate


Isoaspartic acid is an aspartic acid residue isomeric to the typical α peptide linkage. It is a β-amino acid, with the side chain carboxyl moved to the backbone. Such a change is caused by a chemical reaction in which the nitrogen atom on the N+1 following peptide bond nucleophilically attacks the γ-carbon of the side chain of an asparagine or aspartic acid residue, forming a succinimide intermediate. Hydrolysis of the intermediate results in two products, either aspartic acid or isoaspartic acid, which is a β-amino acid. The reaction also results in the deamidation of the asparagine residue. Racemization may occur leading to the formation of D-aminoacids.

Kinetics of isoaspartyl formation

Isoaspartyl formation reactions have been conjectured to be one of the factors that limit the useful lifetime of proteins.
Isoaspartyl formation proceeds much more quickly if the asparagine is followed by a small, flexible residue that leaves the peptide group open for attack. These reactions also proceed much more quickly at elevated pH and temperatures.

Repair

repairs isoaspartate and D-aspartate residues by sticking a methyl group onto the side chain carboxyl group in the residue, creating an ester. The ester rapidly and spontaneously turns into the succinimide, and randomly turns back into normal aspartic acid or isoaspartate again for another attempt.