High impact information on Pcmt

• Protein L-isoaspartyl methyltransferases (PIMT; EC 2.1.1.77) catalyze the S-adenosylmethionine-dependent methylation of L-isoaspartyl residues that arise spontaneously in proteins with age, thereby initiating a repair process that restores the normal backbone configuration to the damaged polypeptide [1].
• Effectively, this displacement generates a more open conformation that allows greater solvent access to S-adenosylhomocysteine, which is almost completely buried in other PIMT structures [1].
• Catalysis by dPIMT requires the side chain of the conserved, active site residue Ser-60, since substitution of this residue with Thr, Gln, or Ala reduces or abolishes the methylation of both protein and isoaspartyl peptide substrates [1].
• A single 1.4-kb Pcmt transcript is detected in RNA preparations from embryos, larvae, pupae and adults [2].
• Urea feeding tended to increase PIMT activity in both control and urea-tolerant populations [3].

Analytical, diagnostic and therapeutic context of Pcmt

• To understand structural features of the Drosophila PIMT (dPIMT) important for catalysis, the crystal structure of dPIMT was determined at a resolution of 2.2 A, and site-directed mutagenesis was used to identify the role of Ser-60 in catalysis [1].

References