EUKARYOTIC PROTEIN CARBOXYL METHYLTRANSFE RASES - 2 DISTINCT CLASSES OF ENZYMES

Protein carboxyl methyltransferases are ubiquitous enzymes that transf er a methyl group from S-adenosyl-L-methionine (AdoMet) to some carbox yl groups of proteins. In eukaryotic cells, two distinct classes of th ese enzymes have been described to date. One of these, L-isoaspartate/ D-aspartate methyltransferases, recognizes with high affinity damaged aspartic acid residues that originate mainly from spontaneous deamidat ion of asparagine residues and from racemisation of aspartate residues . These enzymes exist as molecular species of 27 kDa and a number of i soforms have been identified. In all cases, these enzymes are non-spec ific and the methyl esters formed by their action are highly sensitive to moderate alkaline conditions. Numerous studies have suggested that these enzymes may be involved in the repair of the altered residues, as reflected by the repair of various isoaspartate-containing peptides and some proteins following incubation with AdoMet and purified carbo xyl methyltransferases. The other class of methyltransferases, the C-t erminal carboxyl methyltransferases, catalyze the methylation of the c arboxyl group of isoprenylated cysteine residues located in the C-term inal portion of various proteins, including members of the Ras superfa mily of GTP-binding proteins. The post-translational modification of t hese proteins by isoprenylation and carboxyl methylation is supposed t o play a major role in their association with cellular membranes, wher e they become physiologically active. In addition, recent studies have suggested that the methylation of isoprenylated proteins may play an important function in promoting specific interactions between these pr oteins and specific effectors located in the membrane.