KEGG   ENZYME: 2.1.1.224Help
Entry
EC 2.1.1.224                Enzyme                                 

Name
23S rRNA (adenine2503-C8)-methyltransferase;
Cfr (gene name)
Class
Transferases;
Transferring one-carbon groups;
Methyltransferases
BRITE hierarchy
Sysname
S-adenosyl-L-methionine:23S rRNA (adenine2503-C8)-methyltransferase
Reaction(IUBMB)
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
Substrate
S-adenosyl-L-methionine [CPD:C00019];
adenine2503 in 23S rRNA;
reduced [2Fe-2S] ferredoxin
Product
S-adenosyl-L-homocysteine [CPD:C00021];
L-methionine [CPD:C00073];
5'-deoxyadenosine [CPD:C05198];
8-methyladenine2503 in 23S rRNA;
oxidized [2Fe-2S] ferredoxin
Comment
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].
History
EC 2.1.1.224 created 2011, modified 2014
Orthology
K15632  23S rRNA (adenine-C8)-methyltransferase
Genes
SAMY: DB32_002551
LLU: AKJ09_01684
BAY: RBAM_005660
BAQ: BACAU_0492(cfr)
BAMP: B938_02600
BAML: BAM5036_0497(cfr)
BAMA: RBAU_0529(cfr)
BAMN: BASU_0521(cfr)
BAMB: BAPNAU_0497(YloN1)
BAMT: AJ82_03155
BMP: NG74_00546(cfr)
BAO: BAMF_0476(RBAM_005660)
BQL: LL3_00507
BAMI: KSO_016870
BAMC: U471_05350
BAMF: U722_02850
BCL: ABC1074
BACP: SB24_07020
BLR: BRLA_c030110(cfr)
PSAB: PSAB_12585
TAB: CIG75_03920(cfr)
CBO: CBO2857(cfr)
CBA: CLB_2801
CBH: CLC_2734
CBY: CLM_3236
CBL: CLK_2251
CBB: CLD_1710
CBI: CLJ_B3097
CBF: CLI_2911
CBM: CBF_2902
CSR: Cspa_c21050(rlmN2)
CPAT: CLPA_c34520(cfr)
CPAE: CPAST_c34520(cfr)
CPY: Cphy_2221
CAD: Curi_c04560(cfr)
 » show all
Taxonomy
Reference
1  [PMID:19144912]
  Authors
Giessing AM, Jensen SS, Rasmussen A, Hansen LH, Gondela A, Long K, Vester B, Kirpekar F
  Title
Identification of 8-methyladenosine as the modification catalyzed by the radical  SAM methyltransferase Cfr that confers antibiotic resistance in bacteria.
  Journal
RNA 15:327-36 (2009)
DOI:10.1261/rna.1371409
  Sequence
Reference
2  [PMID:20007606]
  Authors
Kaminska KH, Purta E, Hansen LH, Bujnicki JM, Vester B, Long KS
  Title
Insights into the structure, function and evolution of the radical-SAM 23S rRNA methyltransferase Cfr that confers antibiotic resistance in bacteria.
  Journal
Nucleic Acids Res 38:1652-63 (2010)
DOI:10.1093/nar/gkp1142
Reference
3  [PMID:20184321]
  Authors
Yan F, LaMarre JM, Rohrich R, Wiesner J, Jomaa H, Mankin AS, Fujimori DG
  Title
RlmN and Cfr are radical SAM enzymes involved in methylation of ribosomal RNA.
  Journal
J Am Chem Soc 132:3953-64 (2010)
DOI:10.1021/ja910850y
Reference
4  [PMID:21368151]
  Authors
Yan F, Fujimori DG
  Title
RNA methylation by radical SAM enzymes RlmN and Cfr proceeds via methylene transfer and hydride shift.
  Journal
Proc Natl Acad Sci U S A 108:3930-4 (2011)
DOI:10.1073/pnas.1017781108
Reference
5  [PMID:21415317]
  Authors
Grove TL, Benner JS, Radle MI, Ahlum JH, Landgraf BJ, Krebs C, Booker SJ
  Title
A radically different mechanism for S-adenosylmethionine-dependent methyltransferases.
  Journal
Science 332:604-7 (2011)
DOI:10.1126/science.1200877
Reference
6  [PMID:21527678]
  Authors
Boal AK, Grove TL, McLaughlin MI, Yennawar NH, Booker SJ, Rosenzweig AC
  Title
Structural basis for methyl transfer by a radical SAM enzyme.
  Journal
Science 332:1089-92 (2011)
DOI:10.1126/science.1205358
Reference
7  [PMID:21916495]
  Authors
Grove TL, Radle MI, Krebs C, Booker SJ
  Title
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.
  Journal
J Am Chem Soc 133:19586-9 (2011)
DOI:10.1021/ja207327v
Reference
8  [PMID:23644479]
  Authors
Grove TL, Livada J, Schwalm EL, Green MT, Booker SJ, Silakov A
  Title
A substrate radical intermediate in catalysis by the antibiotic resistance protein Cfr.
  Journal
Nat Chem Biol 9:422-7 (2013)
DOI:10.1038/nchembio.1251
Other DBs
ExplorEnz - The Enzyme Database: 2.1.1.224
IUBMB Enzyme Nomenclature: 2.1.1.224
ExPASy - ENZYME nomenclature database: 2.1.1.224
BRENDA, the Enzyme Database: 2.1.1.224

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