Recognition of age-damaged (R,S)-adenosyl-L-methionine by two methyltransferases in the yeast Saccharomyces cerevisiae.
The biological methyl donor S-adenosylmethionine (AdoMet) can exist in two diastereoisomeric states with respect to its sulfonium ion. The S configuration, (S,S)-AdoMet, is the only form that is produced enzymatically as well as the only form used in almost all biological methylation reactions. Under physiological conditions, however, the sulfonium ion can spontaneously racemize to the R form, producing (R,S)-AdoMet. As of yet, (R,S)-AdoMet has no known physiological function and may inhibit cellular reactions. In this study, we found two Saccharomyces cerevisiae enzymes that are capable of recognizing (R,S)-AdoMet and using it to methylate homocysteine to form methionine. These enzymes are the products of the SAM4 and MHT1 genes, identified previously as homocysteine methyltransferases dependent upon AdoMet and S-methylmethionine, respectively. We found here that Sam4 recognizes both (S,S)- and (R,S)-AdoMet, but that its activity is much higher with the R,S form. Mht1 reacts with only the R,S form of AdoMet, whereas no activity is seen with the S,S form. R,S-Specific homocysteine methyltransferase activity is also shown here to occur in extracts of Arabidopsis thaliana, Drosophila melanogaster, and Caenorhabditis elegans, but has not been detected in several tissue extracts of Mus musculus. Such activity may function to prevent the accumulation of (R,S)-AdoMet in these organisms.
Vinci
Chris R
CR
Department of Chemistry and Biochemistry and the Molecular Biology Institute, UCLA, Los Angeles, California 90095-1569, USA.
Clarke
Steven G
SG
D000595:Amino Acid Sequence; D000818:Animals; D017360:Arabidopsis / Q000201:enzymology; D017173:Caenorhabditis elegans / Q000201:enzymology; D004331:Drosophila melanogaster / Q000201:enzymology; D006710:Homocysteine / Q000737:chemistry; D050904:Homocysteine S-Methyltransferase / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008715:Methionine / Q000737:chemistry; D008780:Methyltransferases / Q000737:chemistry*; D051379:Mice; D008969:Molecular Sequence Data; D012436:S-Adenosylmethionine / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D029701:Saccharomyces cerevisiae Proteins; D006710:Homocysteine; D012436:S-Adenosylmethionine; D008715:Methionine; D008780:Methyltransferases; D050904:Homocysteine S-Methyltransferase; C519167:MHT1 protein, S cerevisiae; C519166:SAM4 protein, S cerevisiae