protein-L-isoaspartate (D-aspartate) O-methyltransferase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: S-adenosyl-L-methionine + protein L-beta-aspartate = S-adenosyl-L-homocysteine + protein L-beta-aspartate methyl ester. [EC:2.1.1.77]

Protein-L-isoaspartate (D-aspartate) O-methyltransferase activity is a critical enzymatic function that plays a vital role in the repair of damaged proteins. Specifically, it targets and repairs L-isoaspartate and D-aspartate residues within proteins, which are non-canonical amino acids that arise due to spontaneous deamidation of asparagine and aspartate residues. This deamidation process can lead to protein misfolding, aggregation, and loss of function, contributing to aging and various age-related diseases.

The enzyme, known as protein-L-isoaspartate (D-aspartate) O-methyltransferase (PIMT), utilizes S-adenosyl-L-methionine (SAM) as a methyl donor to catalyze the transfer of a methyl group to the carboxyl group of L-isoaspartate or D-aspartate residues. This methylation step converts the non-canonical amino acid into a more stable derivative, allowing for the protein to be recognized and processed by other cellular repair machinery.

The repair process typically involves the following steps:

1. PIMT recognizes and binds to the L-isoaspartate or D-aspartate residue within the damaged protein.
2. The enzyme utilizes SAM as a methyl donor, transferring a methyl group to the carboxyl group of the non-canonical amino acid.
3. This methylation step converts the L-isoaspartate or D-aspartate residue into a more stable derivative.
4. The modified protein is then recognized and processed by other cellular repair machinery, which can either remove the damaged residue or restore the correct amino acid sequence.

PIMT activity is essential for maintaining protein homeostasis and protecting against the accumulation of damaged proteins. Its deficiency can lead to various cellular dysfunction and contribute to the development of age-related diseases such as Alzheimer's disease, Parkinson's disease, and cancer. The activity of this enzyme is therefore crucial for cellular health and longevity.'
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Proteins (2)

Compounds (2)