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].
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.
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.
