ExplorEnz: EC 2.1.1.224

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2.1.1.224

Accepted name:

23S rRNA (adenine²⁵⁰³-C⁸)-methyltransferase

Reaction:

2 S-adenosyl-L-methionine + adenine²⁵⁰³ in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin = S-adenosyl-L-homocysteine + L-methionine + 5′-deoxyadenosine + 8-methyladenine²⁵⁰³ in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin

Other name(s):

Cfr (gene name)

Systematic name:

S-adenosyl-L-methionine:23S rRNA (adenine²⁵⁰³-C⁸)-methyltransferase

Comments:

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 [3,6,7]. 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 2.1.1.192 [23S rRNA (adenine²⁵⁰³-C²)-methyltransferase].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, MetaCyc

References:

1.	Giessing, A.M., Jensen, S.S., Rasmussen, A., Hansen, L.H., Gondela, A., Long, K., Vester, B. and Kirpekar, F. Identification of 8-methyladenosine as the modification catalyzed by the radical SAM methyltransferase Cfr that confers antibiotic resistance in bacteria. RNA 15 (2009) 327–336. [DOI] [PMID: 19144912]
2.	Kaminska, K.H., Purta, E., Hansen, L.H., Bujnicki, J.M., Vester, B. and 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 (2010) 1652–1663. [DOI] [PMID: 20007606]
3.	Yan, F., LaMarre, J.M., Röhrich, R., Wiesner, J., Jomaa, H., Mankin, A.S. and Fujimori, D.G. RlmN and Cfr are radical SAM enzymes involved in methylation of ribosomal RNA. J. Am. Chem. Soc. 132 (2010) 3953–3964. [DOI] [PMID: 20184321]
4.	Yan, F. and 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 (2011) 3930–3934. [DOI] [PMID: 21368151]
5.	Grove, T.L., Benner, J.S., Radle, M.I., Ahlum, J.H., Landgraf, B.J., Krebs, C. and Booker, S.J. A radically different mechanism for S-adenosylmethionine-dependent methyltransferases. Science 332 (2011) 604–607. [DOI] [PMID: 21415317]
6.	Boal, A.K., Grove, T.L., McLaughlin, M.I., Yennawar, N.H., Booker, S.J. and Rosenzweig, A.C. Structural basis for methyl transfer by a radical SAM enzyme. Science 332 (2011) 1089–1092. [DOI] [PMID: 21527678]
7.	Grove, T.L., Radle, M.I., Krebs, C. and Booker, S.J. Cfr and RlmN contain a single [4Fe-4S] cluster, which directs two distinct reactivities for S-adenosylmethionine: methyl transfer by S_N2 displacement and radical generation. J. Am. Chem. Soc. 133 (2011) 19586–19589. [DOI] [PMID: 21916495]
8.	Grove, T.L., Livada, J., Schwalm, E.L., Green, M.T., Booker, S.J. and Silakov, A. A substrate radical intermediate in catalysis by the antibiotic resistance protein Cfr. Nat. Chem. Biol. 9 (2013) 422–427. [DOI] [PMID: 23644479]

[EC 2.1.1.224 created 2011, modified 2014]