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-S] 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 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: 
LLU: 
BAY: 
BAQ: 
BAMP: 
BAML: 
BAMA: 
BAMN: 
BAMB: 
BAMT: 
BMP: 
BAO: 
BAMF_0476(RBAM_005660)
BAZ: 
BQL: 
BXH: 
BAMI: 
BAMC: 
BAMF: 
BCL: 
BACP: 
BBE: 
BLR: 
GYM: 
PSAB: 
PDU: 
PBJ: 
CBO: 
CBO2857(cfr)
CBA: 
CBH: 
CBY: 
CBL: 
CBB: 
CBI: 
CBF: 
CBM: 
CBJ: 
CSR: 
CPAT: 
CPAE: 
CPY: 
CAD: 
 » 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 (2009) 327-36.
  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 (2010) 1652-63.
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 (2010) 3953-64.
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 (2011) 3930-4.
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 (2011) 604-7.
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 (2011) 1089-92.
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 (2011) 19586-9.
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 (2013) 422-7.
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 

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