Modification of Isoaspartyl Peptides and Proteins by Protein Carboxyl Methyltransferase from Bovine Brain
Recent findings indicate that protein carboxyl methyltransfer-ases (PCMTs) from mammalian brain and erythrocytes selectively and stoichiometrically methylate peptides and proteins which contain L-isoaspartyl (isoAsp) sites, i. e., aspartate which is linked via its side-chain β -carboxyl group, rather than via the typical α-carboxyl linkage (reviewed in reference 1). Why would an enzyme exhibit such an unusual specificity? As described below, we have undertaken several approaches to this question. First, we have explored the effect of sequence on the specificity of PCMT for isoAsp-containing peptides. Second, we have studied the effects of methylation on the structure and activity of isoAsp-containing peptides and proteins. Third, we have begun investigating possible sources of isoAsp under in vivo conditions. Our findings to date suggest that PCMT may play a role in the repair or degradation of isoAsp-bearing proteins which arise as a result of spontaneous deamidation of intrinsically labile asparagine sites.
KeywordsPartial Repair Cyclic Imide Normal Peptide Methyl Acceptor Protein Carboxyl
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- 3.Paik, W.K. and Kim, S. (1980) in Protein Methylation, John Wiley and Sons, New YorkGoogle Scholar
- 9.Lowenson, J. and Clarke, S. (1987) Protein carboxyl methyltransferase from human erythroxytes: substrate specificity with L-isoaspartyl and D-aspartyl-containing peptides and proteins. Fed. Proceed.46, 2090Google Scholar
- 14.Murray, E.D., Jr. and Clarke, S. (1985) Metabolism of a synthetic L-isoaspartyl-containing hexapeptide in erythrocyte extracts. Enzymatic methyl esterification is followed by nonenzymatic succinimide formation. J. Biol. Chem. 261, 306–312Google Scholar
- 17.Johnson, B.A., Langmack, E.L. and Aswad, D.W. (1987) Partial repair of deamidation-damaged calmodulin by protein carboxyl methyltransferase. J. Biol. Chem. in pressGoogle Scholar