Comprehensive structural and substrate specificity classification of the saccharomyces cerevisiae methyltransferome

Tomasz Wlodarski, Jan Kutner, Joanna Towpik, Lukasz Knizewski, Leszek Rychlewski, Andrzej Kudlicki, Malgorzata Rowicka-Kudlicka, Andrzej Dziembowski, Krzysztof Ginalski

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Methylation is one of the most common chemical modifications of biologically active molecules and it occurs in all life forms. Its functional role is very diverse and involves many essential cellular processes, such as signal transduction, transcriptional control, biosynthesis, and metabolism. Here, we provide further insight into the enzymatic methylation in S. cerevisiae by conducting a comprehensive structural and functional survey of all the methyltransferases encoded in its genome. Using distant homology detection and fold recognition, we found that the S. cerevisiae methyltransferome comprises 86 MTases (53 well-known and 33 putative with unknown substrate specificity). Structural classification of their catalytic domains shows that these enzymes may adopt nine different folds, the most common being the Rossmann-like. We also analyzed the domain architecture of these proteins and identified several new domain contexts. Interestingly, we found that the majority of MTase genes are periodically expressed during yeast metabolic cycle. This finding, together with calculated isoelectric point, fold assignment and cellular localization, was used to develop a novel approach for predicting substrate specificity. Using this approach, we predicted the general substrates for 24 of 33 putative MTases and confirmed these predictions experimentally in both cases tested. Finally, we show that, in S. cerevisiae, methylation is carried out by 34 RNA MTases, 32 protein MTases, eight small molecule MTases, three lipid MTases, and nine MTases with still unknown substrate specificity.

Original languageEnglish (US)
Article numbere23168
JournalPLoS One
Volume6
Issue number8
DOIs
StatePublished - 2011

Fingerprint

substrate specificity
Substrate Specificity
methylation
Yeast
Methylation
Saccharomyces cerevisiae
taxonomy
Substrates
Genes
Isoelectric Point
methyltransferases
Methyltransferases
isoelectric point
active sites
Signal transduction
Molecules
signal transduction
Signal Transduction
Biosynthesis
Catalytic Domain

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Wlodarski, T., Kutner, J., Towpik, J., Knizewski, L., Rychlewski, L., Kudlicki, A., ... Ginalski, K. (2011). Comprehensive structural and substrate specificity classification of the saccharomyces cerevisiae methyltransferome. PLoS One, 6(8), [e23168]. https://doi.org/10.1371/journal.pone.0023168

Comprehensive structural and substrate specificity classification of the saccharomyces cerevisiae methyltransferome. / Wlodarski, Tomasz; Kutner, Jan; Towpik, Joanna; Knizewski, Lukasz; Rychlewski, Leszek; Kudlicki, Andrzej; Rowicka-Kudlicka, Malgorzata; Dziembowski, Andrzej; Ginalski, Krzysztof.

In: PLoS One, Vol. 6, No. 8, e23168, 2011.

Research output: Contribution to journalArticle

Wlodarski, T, Kutner, J, Towpik, J, Knizewski, L, Rychlewski, L, Kudlicki, A, Rowicka-Kudlicka, M, Dziembowski, A & Ginalski, K 2011, 'Comprehensive structural and substrate specificity classification of the saccharomyces cerevisiae methyltransferome', PLoS One, vol. 6, no. 8, e23168. https://doi.org/10.1371/journal.pone.0023168
Wlodarski, Tomasz ; Kutner, Jan ; Towpik, Joanna ; Knizewski, Lukasz ; Rychlewski, Leszek ; Kudlicki, Andrzej ; Rowicka-Kudlicka, Malgorzata ; Dziembowski, Andrzej ; Ginalski, Krzysztof. / Comprehensive structural and substrate specificity classification of the saccharomyces cerevisiae methyltransferome. In: PLoS One. 2011 ; Vol. 6, No. 8.
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