Abstract
We have analyzed existing methodologies and created novel methodologies for the automatic assignment of S-adenosylmethionine (AdoMet)-dependent methyltransferase functionality to genomic open reading frames based on predicted protein sequences. A large class of the AdoMet-dependent methyltransferases shares a common binding motif for the AdoMet cofactor in the form of a seven-strand twisted beta-sheet; this structural similarity is mirrored in a degenerate sequence similarity that we refer to as methyltransferase signature motifs. These motifs are the basis of our assignments. We find that simple pattern matching based on the motif sequence is of limited utility and that a new method of "sensitized matrices for scoring methyltransferases" (SM2) produced with modified versions of the MEME and MAST tools gives greatly improved results for the Saccharomyces cerevisiae yeast genome. From our analysis, we conclude that this class of methyltransferases makes up approximately 0.6-1.6% of the genes in the yeast, human, mouse, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, and Escherichia coli genomes. We provide lists of unidentified genes that we consider to have a high probability of being methyltransferases for future biochemical analyses.
Highlights
We have analyzed existing methodologies and created novel methodologies for the automatic assignment of Sadenosylmethionine (AdoMet)-dependent methyltransferase functionality to genomic open reading frames based on predicted protein sequences
We have developed semi-automated methods that order the encoded amino acid sequences of the open reading frames of a genome in terms of their likelihood of being Class I methyltransferases
Using the criteria of getting as many of the known methyltransferases in our list as possible while, at the same time, keeping the number of known false positives to a minimum, we have identified candidate methyltransferases in yeast and other organisms
Summary
We have analyzed existing methodologies and created novel methodologies for the automatic assignment of Sadenosylmethionine (AdoMet)-dependent methyltransferase functionality to genomic open reading frames based on predicted protein sequences. A large class of the AdoMet-dependent methyltransferases shares a common binding motif for the AdoMet cofactor in the form of a seven-strand twisted -sheet; this structural similarity is mirrored in a degenerate sequence similarity that we refer to as methyltransferase signature motifs These motifs are the basis of our assignments. The common motifs for Class I AdoMet-dependent methyltransferases were first recognized in 1989 when three regions of similarity were noticed between the protein L-isoaspartyl O-methyltransferase and certain nucleic acid and small molecule methyltransferases [8] Over the years, these regions were expanded, largely by manual inspection of sequences, into Motif I, Post I, Motif II, and Motif III [9]. The result of the 1999 analysis was a list of 26 candidate S. cerevisiae open reading frames (ORFs)
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