Volume 10 Supplement 13

Highlights from the Fifth International Society for Computational Biology (ISCB) Student Council Symposium

Open Access

Computational methods to identify novel methyltransferases

  • Tanya C Petrossian1 and
  • Steven G Clarke1
BMC Bioinformatics200910(Suppl 13):P7

DOI: 10.1186/1471-2105-10-S13-P7

Published: 19 October 2009

Background

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 [1]. 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 [2]. Recently we have used a combination of a new search algorithm and structural information to refine this analysis [3]. 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 [5]. Sequence similarity networks are then used to predict the probable substrates for the putative methyltransferases [3]. 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 [1].

Conclusion

The putative list of methyltransferases for S. cerevisiae among four of the methyltransferases families are italicized (see Table 1). Known methyltransferases are shown for only the SET and SPOUT families. Several putative methyltransferases are found to bind AdoMet through UV-crosslinking experiments (designated * in Table 1). This approach validated previously suggested putative enzymes and additionally identified several new candidates [3]. Extending this analysis to the human proteome surprisingly reveals little expansion of family members (Figure 1). Our goal is to enhance the functional identification of novel methyltransferases by providing lists of the best candidates for biochemical analyses.
https://static-content.springer.com/image/art%3A10.1186%2F1471-2105-10-S13-P7/MediaObjects/12859_2009_Article_3435_Fig1_HTML.jpg
Figure 1

Comparison of the number of known and putative yeast and human methyltransferases in several families.

Table 1

Proteins classified into four families of methyltransferases

Seven-Beta Strand (Class I) (Not shown here are 33 known species)

SET

SPOUT

N6-Adenosine

YBR141C

YLR137W

Set1

Trm10

Ime4

YBR225W

YMR209C*

Set2

Mrm1

Kar4

YBR261C*

YMR228W

Set3

Trm3

YGR001C

YBR271W

YNL022C

Set4

Emg1

 

YDR316W

YNL024C

Set5

YGR283C

 

YHR209W*

YNL092W

Set6

YMR310C

 

YIL064W

YOR239W

Rkm1

YOR021C

 

YIL110W

 

Rkm2

  

YJR129C*

 

Rkm3

  

YKL155C*

 

Rkm4

  

YKL162C

 

Ctm1

  

YLR063W

 

YHL039W

  

Declarations

Acknowledgements

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.

Authors’ Affiliations

(1)
Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California

References

  1. Petrossian TC, Clarke SG: Bioinformatic identification of novel methyltransferases. Epigenomics 2009, in press.Google Scholar
  2. Katz JE, Dlakić M, Clarke S: Automated identification of putative methyltransferaess from genomic open reading frames. Mol Cell Proteomics 2003, 2: 525–540.PubMedGoogle Scholar
  3. Petrossian TC, Clarke SG: Multiple Motif Scanning to identify methyltransferases from the yeast proteome. Mol. Cell. Proteomics 2009, 8: 1516–1526. 10.1074/mcp.M900025-MCP200PubMed CentralView ArticlePubMedGoogle Scholar
  4. Multiple Motif Scanning[http://www.chem.ucla.edu/files/MotifSetup.Zip]
  5. Söding J, Biegert A, Lupas AN: The HHpred interactive server for protein homology detection and structure prediction. Nucleic Acids Res 2005, 33: W244-W248. 10.1093/nar/gki408PubMed CentralView ArticlePubMedGoogle Scholar

Copyright

© Petrossian and Clarke; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.

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