isoaspartic

Isoaspartic, or isoaspartyl, refers to a form of the amino acid aspartic acid found in proteins in which the backbone is linked through the beta-carboxyl group of the residue, creating a beta-aspartyl linkage. This isoaspartyl residue arises when asparagine residues deamidate or when aspartate residues undergo isomerization, producing a beta-linked isoaspartate within the polypeptide chain.

Isoaspartyl formation is a spontaneous post-translational modification that can disrupt protein structure and function by introducing a backbone bend and altering local geometry and charge. The resulting isoaspartate can accumulate in long-lived or stressed proteins, contributing to protein aging and, in some contexts, impaired protein turnover.

Cells repair isoaspartyl residues via the enzyme protein L-isoaspartyl methyltransferase (PIMT; encoded by the PCMT1 gene). PIMT recognizes isoaspartyl sites and methylates the alpha-carboxyl group, promoting spontaneous conversion back to normal aspartate or to asparagine, thereby restoring the original sequence. The repair pathway is conserved and plays a role in protein maintenance, especially in tissues with slow protein turnover.

In research, isoaspartyl content is studied as a biomarker of protein aging and is analyzed using mass spectrometry and antibody-based methods. Its presence has been examined in various proteins, including lens crystallins, collagen, and signaling proteins, in the context of aging and disease.