Isoaspartate

Isoaspartyl formation reaction of Asn-Gly (top right) to Asp-Gly (at left) or iso(Asp)-Gly (in green at bottom right).

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 on the N+1 following peptide bond (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 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).[1] The reaction also results in the deamidation of the asparagine residue. Racemization may occur leading to the formation of D-aminoacids.[2]

Kinetics of isoaspartyl formation

Isoaspartyl formation reactions have been conjectured to be one of the factors that limit the useful lifetime of proteins.[3]

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.

References

  1. ↑ Clarke S. (1987) "Propensity for spontaneous succinimide formation from aspartyl and asparaginyl residues in cellular proteins", Int. J., Peptide Protein Res., 30, 808-821.
  2. ↑ Yang H. & Zubarev R.A. (2010) "Mass spectrometric analysis of asparagine deamidation and aspartate isomerization in polypeptides", Electrophoresis, 31, 1764–1772.
  3. ↑ Stephenson RC and Clarke S. (1989) "Succinimide Formation from Aspartyl and Asparaginyl Peptides as a Model for the Spontaneous Degradation of Proteins", J. Biol. Chem., 264, 6164-6170.
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