WIDESPREAD OCCURRENCE OF 3 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 pro tein and small-molecule S-adenosylmethionine-dependent methyltransfera ses. Using multiple alignments, we have now identified these three reg ions in a much broader group of methyltransferases and have used these data to define a consensus for each region. Of the 84 non-DNA methylt ransferase 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 descr ibed 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 46 of these enzymes, and an additional 15 have mo tifs I and III. The motifs are always found in the same order on the p olypeptide chain and are separated by comparable intervals. We suggest that these conserved regions contribute to the binding of the substra te S-adenosylmethionine and/or the product S-adenosylhomocysteine. The se motifs can also be identified in certain nonmethyltransferases that utilize either S-adenosylmethionine or S-adenosylhomocysteine,includi ng S-adenosylmethionine decarboxylase, S-adenosylmethionine synthetase , and S-adenosylhomocysteine hydrolase. In the latter two types of enz ymes, motif I is similar to the conserved nucleotide binding motif of protein kinases and other nucleotide binding proteins. These motifs ma y be of use in predicting methyltransferases and related enzymes from the open reading frames generated by genomic sequencing projects. (C) 1994 Academic Press, Inc.