Widespread occurrence of three sequence motifs in diverse S-adenosylmethionine-dependent methyltransferases suggests a common structure for these enzymes.
Three regions of sequence similarity have been reported in several protein and small-molecule S-adenosylmethionine-dependent methyltransferases. Using multiple alignments, we have now identified these three regions in a much broader group of methyltransferases and have used these data to define a consensus for each region. Of the 84 non-DNA methyltransferase sequences in the GenBank, NBRF PIR, and Swissprot databases comprising 37 distinct enzymes, we have found 69 sequences possessing motif I. This motif is similar to a conserved region previously described in DNA adenine and cytosine methyltransferases. Motif II is found in 46 sequences, while motif III is found in 61 sequences. All three regions are found in 45 of these enzymes, and an additional 15 have motifs I and III. The motifs are always found in the same order on the polypeptide chain and are separated by comparable intervals. We suggest that these conserved regions contribute to the binding of the substrate S-adenosylmethionine and/or the product S-adenosylhomocysteine. These motifs can also be identified in certain nonmethyltransferases that utilize either S-adenosylmethionine or S-adenosylhomocysteine, including S-adenosylmethionine decarboxylase, S-adenosylmethionine synthetase, and S-adenosylhomocysteine hydrolase. In the latter two types of enzymes, motif I is similar to the conserved nucleotide binding motif of protein kinases and other nucleotide binding proteins. These motifs may be of use in predicting methyltransferases and related enzymes from the open reading frames generated by genomic sequencing projects.
Kagan
R M
RM
Department of Chemistry and Biochemistry, University of California, Los Angeles 90024-1569.
Clarke
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria / Q000201:enzymology; D016384:Consensus Sequence; D016208:Databases, Factual; D005796:Genes; D006801:Humans; D008780:Methyltransferases / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D012436:S-Adenosylmethionine / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D012436:S-Adenosylmethionine; D008780:Methyltransferases