Mammalian brain and erythrocyte carboxyl methyltransferases are similar enzymes that recognize both D-aspartyl and L-isoaspartyl residues in structurally altered protein substrates.
Two purified isozymes of protein carboxyl methyltransferase from bovine brain catalyze the substoichiometric transfer of methyl groups in vitro from S-adenosyl-L-[methyl-3H]methionine to several erythrocyte membrane proteins, which include bands 2.1, 3, and 4.1, as well as several integral membrane polypeptides. D-Aspartic acid beta-[3H]methyl ester has been isolated from proteolytic digests of these methylated proteins, suggesting that protein D-aspartyl residues can serve as methyl-acceptor sites for the two brain enzymes. This formation of D-aspartic acid beta-[3H]methyl ester is competitively inhibited by the peptide L-Val-L-Tyr-L-Pro-L-isoAsp-Gly-L-Ala, which contains an L-aspartyl residue in an unusual beta-peptide linkage. Since this peptide is a stoichiometric substrate for the brain methyltransferases, it appears that one enzymatic activity can catalyze methyl ester formation at both D-aspartyl and L-isoaspartyl sites. In these respects, the activity of both brain isozymes closely resembles those previously described for the erythrocyte enzyme. The results are discussed in terms of a model in which derivatized aspartyl residues in proteins, arising by either racemization or isomerization, are recognized by the methyltransferase; the enzyme may function in either the metabolism or correction of the altered structures. The presence of a similar enzyme in both translationally active (brain) and inactive (erythrocyte) tissues suggests that the reactions are of general importance to cellular integrity.
D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D001921:Brain / Q000201:enzymology*; D002417:Cattle; D004912:Erythrocytes / Q000201:enzymology*; D007527:Isoenzymes / Q000302:isolation & purification / Q000378:metabolism; D007536:Isomerism; D007700:Kinetics; D008565:Membrane Proteins / Q000097:blood; D008745:Methylation; D009842:Oligopeptides / Q000494:pharmacology; D011496:Protein Methyltransferases / Q000378:metabolism*; D011497:Protein O-Methyltransferase / Q000302:isolation & purification / Q000378:metabolism*; D013379:Substrate Specificity
D007527:Isoenzymes; D008565:Membrane Proteins; D009842:Oligopeptides; D001224:Aspartic Acid; D011496:Protein Methyltransferases; D011497:Protein O-Methyltransferase