EC - 23S rRNA (adenine2503-C8)-methyltransferase

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IntEnz Enzyme Nomenclature


Accepted name:
23S rRNA (adenine2503-C8)-methyltransferase
Other name:
Cfr (gene name)
Systematic name:
S-adenosyl-L-methionine:23S rRNA (adenine2503-C8)-methyltransferase




This enzyme is a member of the 'AdoMet radical' (radical SAM) family. S-adenosyl-L-methionine acts as both a radical generator and as the source of the appended methyl group. It contains an [4Fe-4S] cluster [1]. Cfr is an plasmid-acquired methyltransferase that protects cells from the action of antibiotics [1]. The enzyme methylates adenosine at position 2503 of 23S rRNA by a radical mechanism, transferring a CH2 group from S-adenosyl-L-methionine while retaining the hydrogen at the C-8 position of the adenine. Cfr first transfers an CH2 group to a conserved cysteine (Cys338 in Staphylococcus aureus) [7], the generated radical from a second S-adenosyl-L-methionine then attacks the methyl group, exctracting a hydrogen. The formed radical forms a covalent intermediate with the adenine group of the tRNA [8]. The enzyme will also methylate 2-methyladenine produced by the action of EC [23S rRNA (adenine2503-C2)-methyltransferase].

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , UniPathway
Structural data: CSA , EC2PDB
UniProtKB/Swiss-Prot: (11) [show] [UniProt]


  1. Giessing, A. M., Jensen, S. S., Rasmussen, A., Hansen, L. H., Gondela, A., Long, K., Vester, B., Kirpekar, F.
    Identification of 8-methyladenosine as the modification catalyzed by the radical SAM methyltransferase Cfr that confers antibiotic resistance in bacteria.
    RNA 15: 327-336 (2009). [PMID: 19144912]
  2. Kaminska, K. H., Purta, E., Hansen, L. H., Bujnicki, J. M., Vester, B., Long, K. S.
    Insights into the structure, function and evolution of the radical-SAM 23S rRNA methyltransferase Cfr that confers antibiotic resistance in bacteria.
    Nucleic Acids Res. 38: 1652-1663 (2010). [PMID: 20007606]
  3. Yan, F., LaMarre, J. M., Rohrich, R., Wiesner, J., Jomaa, H., Mankin, A. S., Fujimori, D. G.
    RlmN and Cfr are radical SAM enzymes involved in methylation of ribosomal RNA.
    J. Am. Chem. Soc. 132: 3953-3964 (2010). [PMID: 20184321]
  4. Yan, F., Fujimori, D. G.
    RNA methylation by radical SAM enzymes RlmN and Cfr proceeds via methylene transfer and hydride shift.
    Proc. Natl. Acad. Sci. USA 108: 3930-3934 (2011). [PMID: 21368151]
  5. Grove, T. L., Benner, J. S., Radle, M. I., Ahlum, J. H., Landgraf, B. J., Krebs, C., Booker, S. J.
    A radically different mechanism for S-adenosylmethionine-dependent methyltransferases.
    Science 332: 604-607 (2011). [PMID: 21415317]
  6. Boal, A. K., Grove, T. L., McLaughlin, M. I., Yennawar, N. H., Booker, S. J., Rosenzweig, A. C.
    Structural basis for methyl transfer by a radical SAM enzyme.
    Science 332: 1089-1092 (2011). [PMID: 21527678]
  7. Grove, T. L., Radle, M. I., Krebs, C., Booker, S. J.
    Cfr and RlmN contain a single [4Fe-4S] cluster, which directs two distinct reactivities for S-adenosylmethionine: methyl transfer by SN2 displacement and radical generation.
    J. Am. Chem. Soc. 133: 19586-19589 (2011). [PMID: 21916495]
  8. Grove, T. L., Livada, J., Schwalm, E. L., Green, M. T., Booker, S. J., Silakov, A.
    A substrate radical intermediate in catalysis by the antibiotic resistance protein Cfr.
    Nat. Chem. Biol. 9: 422-427 (2013). [PMID: 23644479]

[EC created 2011, modified 2014]