Interaction of the tylosin-resistance methyltransferase RlmA II at its rRNA target differs from the orthologue RlmA I

J Mol Biol. 2008 May 16;378(5):969-75. doi: 10.1016/j.jmb.2008.03.024. Epub 2008 Mar 19.


RlmA(II) methylates the N1-position of nucleotide G748 in hairpin 35 of 23 S rRNA. The resultant methyl group extends into the peptide channel of the 50 S ribosomal subunit and confers resistance to tylosin and other mycinosylated macrolide antibiotics. Methylation at G748 occurs in several groups of Gram-positive bacteria, including the tylosin-producer Streptomyces fradiae and the pathogen Streptococcus pneumoniae. Recombinant S. pneumoniae RlmA(II) was purified and shown to retain its activity and specificity in vitro when tested on unmethylated 23 S rRNA substrates. RlmA(II) makes multiple footprint contacts with nucleotides in stem-loops 33, 34 and 35, and does not interact elsewhere in the rRNA. Binding of RlmA(II) to the rRNA is dependent on the cofactor S-adenosylmethionine (or S-adenosylhomocysteine). RlmA(II) interacts with the same rRNA region as the orthologous enzyme RlmA(I) that methylates at nucleotide G745. Differences in nucleotide contacts within hairpin 35 indicate how the two methyltransferases recognize their distinct targets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / metabolism*
  • Bacterial Proteins* / chemistry
  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / metabolism
  • Drug Resistance, Microbial
  • Methyltransferases* / chemistry
  • Methyltransferases* / genetics
  • Methyltransferases* / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleic Acid Conformation*
  • Protein Conformation*
  • RNA, Ribosomal* / chemistry
  • RNA, Ribosomal* / genetics
  • RNA, Ribosomal* / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Tylosin / metabolism*


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • RNA, Ribosomal
  • Recombinant Proteins
  • Methyltransferases
  • TlrB protein, Streptomyces fradiae
  • Tylosin