Protein L Isoaspartate D Aspartate O Methyltransferase (PIMT) is an enzyme that plays a crucial role in repairing and reversing the damage caused by the formation of isoaspartyl protein damage. Isoaspartyl protein damage occurs when the amino acid aspartate in proteins undergoes a spontaneous chemical conversion to isoaspartate, resulting in the formation of an abnormal peptide bond.
PIMT is responsible for recognizing these damaged proteins and catalyzing the transfer of a methyl group from S-adenosyl-L-methionine to the aspartyl residue, converting the isoaspartate back to aspartate. This methylation process restores the protein's structural integrity and functionality. By repairing the damaged proteins, PIMT actively maintains the overall functional and structural integrity of the proteome.
The activity of PIMT is not limited to repairing isoaspartyl protein damage. It also participates in the recognition and methylation of other D-aspartate residues, as well as the repair of other chemically damaged proteins. This enzyme is usually found in various tissues and is highly conserved across species, indicating its crucial role in maintaining protein homeostasis.
The dysfunction or reduced activity of PIMT has been associated with various age-related diseases, such as neurodegenerative disorders, including Alzheimer's disease. Additionally, PIMT has been suggested to play a role in the regulation of cell cycle progression, DNA repair, and cell apoptosis, highlighting its diverse biological functions beyond protein repair.
Understanding the role and function of PIMT is essential in unraveling the mechanisms behind protein misfolding, aggregation, and aging-related disorders, ultimately contributing to the development of therapeutic strategies for these conditions.
