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Literature summary for 2.1.1.224 extracted from

  • 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 (2011), Science, 332, 1089-1092 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.1.1.224

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin Staphylococcus aureus
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 S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
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 ?

Organism

Organism UniProt Comment Textmining
Staphylococcus aureus A5HBL2
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
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 Staphylococcus aureus S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
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 ?
additional information the enzyme employs a [4Fe-4S] cluster to supply the requisite electron for reductive cleavage of SAM, usually to L-methionine and a 5'-deoxyadenosyl 5'-radical. SAM is the source of both the 5'-deoxyadenosyl 5'-radical and the appended methyl group Staphylococcus aureus ?
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Synonyms

Synonyms Comment Organism
Cfr
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 Staphylococcus aureus

Cofactor

Cofactor Comment Organism Structure
reduced [2Fe-2S] ferredoxin
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 Staphylococcus aureus
S-adenosyl-L-methionine
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 Staphylococcus aureus

General Information

General Information Comment Organism
evolution enzyme Cfr belongs to the radical SAM (RS) superfamily of enzymes, catalysts that use S-adenosyl-L-methionine (SAM) as an oxidant to perform difficult and often complex transformations by radical mechanisms. RS superfamily enzymes employ a [4Fe-4S] cluster to supply the requisite electron for reductive cleavage of SAM, usually to L-methionine and a 5'-deoxyadenosyl 5'-radical. Similar enzyme RlmN (EC 2.1.1.192) is proposed to be an evolutionary precursor to Cfr. Residues conserved among both enzymes in a pairwise alignment of Escherichia coli RlmN and Staphylococcus aureus Cfr are mapped onto the RlmN structure. The catalytic residues in the active site are strictly conserved as are most of the surrounding residues within the core of the barrel, supporting the proposal that the enzymes use a common mechanism for C-methylation. The high degree of sequence conservation near the active site suggests that methylation site specificity during the reaction may be controlled in part by more distant structural elements. In Cfr, two large conformationally flexible regions in the RlmN structure are absent Staphylococcus aureus
evolution RlmN and Cfr belong to the radical SAM (RS) superfamily of enzymes. RlmN is proposed to be an evolutionary precursor to Cfr. The catalytic residues in theactive site are strictly conserved as are most of the surrounding residues within the core of the barrel Staphylococcus aureus
metabolism methyl transfer is essential in the synthesis of cellular metabolites and clinically relevant natural products, and in the modification of RNA, DNA, lipids, and proteins Staphylococcus aureus
additional information structure-function analysis of RlmN from Escherichia coli (EC 2.1.1.192) compared to Cfr, Escherichia coli RlmN and Staphylococcus aureus Cfr are mapped onto the RlmN structure, detailed overview. The Cfr reaction proceeds by a ping-pong mechanism. The methyl group from one SAM molecule is initially appended to a conserved Cys residue by a typical SN2 displacement. This SAM-derived one carbon unit is then attached to the RNA by radical addition initiated by a 5'-deoxyadenosyl 5'-radical formed from a second molecule of SAM. The expected role of the radical is to abstract a hydrogen atom from the substrate, in this case the C8 (Cfr) hydrogen atom from A2503, activating the substrate for subsequent methylation. Finally, this covalent intermediate is resolved by formation of a disulfide bond between the methyl-carrying Cys (mCys) residue and a second conserved Cys residue. Cys 355 is a key catalytic residue that is methylated in the first step of the proposed mechanism Staphylococcus aureus
physiological function the radical SAM (RS) enzymes RlmN and Cfr methylate 23S ribosomal RNA, modifying the C2 or C8 position of adenosine 2503. The methyl groups are installed by a two-step sequence involving initial methylation of a conserved Cys residue (RlmN Cys 355) by SAM. Methyl transfer to the substrate requires reductive cleavage of a second equivalent of SAM. Cfr confers antibiotic resistance by methylating C8 of A2503 Staphylococcus aureus