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

Stephen Douthwaite, Lene Jakobsen, Satoko Yoshizawa, Dominique Fourmy

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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.
Original languageEnglish
JournalJournal of Molecular Biology
Volume378
Issue number5
Pages (from-to)969-975
Number of pages6
ISSN0022-2836
DOIs
Publication statusPublished - 16. May 2008

Keywords

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

Fingerprint

Dive into the research topics of 'Interaction of the tylosin-resistance methyltransferase RlmA II at its rRNA target differs from the orthologue RlmA I'. Together they form a unique fingerprint.

Cite this