Volume 10 Supplement 13
Computational methods to identify novel methyltransferases
© Petrossian and Clarke; licensee BioMed Central Ltd. 2009
Published: 19 October 2009
1.2% of the yeast genes are estimated to encode enzymes that catalyze the transfer of a methyl group from S-adenosylmethionine (AdoMet) to protein, nucleic acid, lipid, and small molecule substrates . These enzymes function in biosynthesis, regulating metabolic pathways, and controlling gene expression, including writing the histone code. BLAST and MEME/MAST analysis using the amino acid sequence of motifs have previously generated a list of putative Class I methyltransferases . Recently we have used a combination of a new search algorithm and structural information to refine this analysis . This study utilizes these updated methods of identifying motifs and scanning the proteome to predict new members of the different families of methyltransferases in different organisms. These new members may function in novel pathways or new modes of regulation.
Materials and methods
Advanced hidden Markov models (HMM) profiles, predicted secondary structures, and solved crystal structures are used to identify the AdoMet-binding motifs of the different families of methyltransferases [1, 3]. To generate a list of putative methyltransferases, we used both our newly developed program "Multiple Motif Scanning" [3, 4] and HHpred . Sequence similarity networks are then used to predict the probable substrates for the putative methyltransferases . Additionally, several of the candidate methyltransferases were incubated with radioactive AdoMet to reveal binding by detection of the radioactive protein-ligand via SDS-PAGE separation .
Proteins classified into four families of methyltransferases
Seven-Beta Strand (Class I) (Not shown here are 33 known species)
This research was supported by the National Institutes of Health Grant GM026020 and the Office of Science (BER), U.S. Department of Energy, Grant No. DE-FG02-06ED64270. T.C.P. was supported by the UCLA Chemistry-Biology Interface Training Grant GM008496.
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This article is published under license to BioMed Central Ltd.