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Literature summary extracted from

  • Pakula, K.K.; Hansen, L.H.; Vester, B.
    Combined effect of the Cfr methyltransferase and ribosomal protein L3 mutations on resistance to ribosome-targeting antibiotics (2017), Antimicrob. Agents Chemother., 61, e00862-17 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.1.1.224 a plasmid-borne cfr geneis transfromed into a uL3-depleted Escherichia coli strain containing either wild-type L3 or L3 with one of seven mutations, G147R, Q148F, N149S, N149D, N149R, Q150L, or T151P, expressed from plasmid-carried rplC genes. The L3 mutations are well tolerated, with small to moderate growth rate decreases. The presence of Cfr has a very minor influence on the growth rate. The transformants show resistance to linezolid, tiamulin, florfenicol, and Synercid (a combination of quinupristin and dalfopristin [Q-D]) Staphylococcus sp.

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.1.1.224 2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin Staphylococcus sp.
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 S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.1.1.224 Staphylococcus sp.
-
 clinical isolate
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.1.1.224 2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin
-
 Staphylococcus sp. S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.1.1.224 Cfr
-
 Staphylococcus sp.
2.1.1.224 Cfr methyltransferase
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 Staphylococcus sp.

Cofactor

EC Number Cofactor Comment Organism Structure
2.1.1.224 S-adenosyl-L-methionine
-
 Staphylococcus sp.

General Information

EC Number General Information Comment Organism
2.1.1.224 metabolism several groups of antibiotics inhibit bacterial growth by binding to bacterial ribosomes. Mutations in ribosomal protein L3 have been associated with resistance to linezolid and tiamulin, which both bind at the peptidyl transferase center in the ribosome. Resistance to these and other antibiotics also occurs through methylation of 23S rRNA at position A2503 by the methyltransferase Cfr. The resistance from Cfr is, in all cases, stronger than the effects of the L3 mutations, but various effects are obtained with the combinations of Cfr and L3 mutations ranging from a synergistic to an antagonistic effect. Linezolid and tiamulin susceptibility vary greatly among the L3 mutations, while no significant effects on florfenicol and Q-D susceptibility are seen. Relative positions of L3 mutations, methylation of the 23S rRNA at position A2503, and antibiotics, three-dimensional structure model, overview. Analysis of antibiotic susceptibilities of the L3 mutant strains with and without Cfr expression Staphylococcus sp.
2.1.1.224 physiological function the cfr gene encodes an rRNA methyltransferase that adds a methyl group at the C-8 position of 23S rRNA nucleotide A2503 at the peptidyl transferase center (PTC) in the ribosome. This m8A2503 modification confers resistance to more than six classes of antibiotics that bind at overlapping nonidentical sites at the PTC Staphylococcus sp.