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Isoaspartic acid (isoaspartate) is an amino acid that is an isomer of aspartic acid. It is formed via a chemical reaction in which the nitrogen atom of the following peptide group (in black at top right of Figure 1) nucleophilically attacks the γ-carbon of the side chain of an asparagine or aspartic acid residue, forming a symmetric succinimide intermediate (in red). Hydrolysis of the intermediate results in two products, either aspartic acid (in black at left) or isoaspartic acid, which is a β-amino acid (in green at bottom right). 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 (such as Gly) that leaves the peptide group open for attack. These reactions also proceed much more quickly at elevated pH (>10) and temperatures.