PCMT1 Human

PIMT recognizes and catalyzes the repair of damaged L-isoaspartyl and D-aspartyl groups in proteins. These damaged residues often result from spontaneous deamidation and isomerization of asparagine and aspartate residues, which can occur as proteins age . The enzyme transfers methyl groups from S-adenosyl-L-methionine to the alpha side chain carboxyl groups of these damaged residues, forming a methyl ester. This methyl ester then undergoes nonenzymatic reactions to form L-succinimide, which can be hydrolyzed to generate repaired L-aspartyl residues .

The repair mechanism facilitated by PIMT is essential for maintaining protein integrity. Without this repair, abnormal aspartyl residues accumulate, leading to the formation of dysfunctional proteins. In mice, the absence of PIMT has been linked to fatal progressive epilepsy, highlighting the enzyme’s critical role in cellular health .

Human recombinant PIMT is produced using recombinant DNA technology, which allows for the expression of the human enzyme in a host organism, such as bacteria or yeast. This recombinant form is used in various research and therapeutic applications to study the enzyme’s function and to develop potential treatments for diseases associated with protein damage.

Mutations in the PCMT1 gene, which encodes PIMT, have been associated with several disorders, including spina bifida and premature ovarian failure . Additionally, the enzyme may play a protective role in the pathogenesis of Alzheimer’s disease, making it a target for therapeutic research .

The enzyme exists in human cytosol in two forms due to alternative splicing and varies among individuals due to a single polymorphism at residue 119, which can be either valine or isoleucine . This structural variation can influence the enzyme’s activity and stability.