Automethylation : a response to enzyme aging

Abstract

This is the first study to explore the ability of an enzyme to recognize and repair spontaneous age-dependent damage to its own sequence. Protein (D-aspartyl/L-isoaspartyl) carboxyl methyltransferase (PCM) is known to repair damage that arises from a spontaneous isomerization of aspartyl and asparaginyl residues in other proteins during aging. As PCM contains several conserved aspartyl and asparaginyl residues, this dissertation tested whether PCM can serve as a methyl acceptor in its own methylation reaction. In investigating the ability of PCM to automethylate, it was discovered that PCM is damaged. The mechanism of this automethylation reaction was determined to be an intermolecular, high affinity, slow turnover reaction and was limited to a subpopulation of damaged PCM molecules, termed αPCM.