The 2.2 A structure of the rRNA methyltransferase ErmC' and its complexes with cofactor and cofactor analogs: implications for the reaction mechanism

J Mol Biol. 1999 Jun 4;289(2):277-91. doi: 10.1006/jmbi.1999.2788.


The rRNA methyltransferase ErmC' transfers methyl groups from S -adenosyl-l-methionine to atom N6 of an adenine base within the peptidyltransferase loop of 23 S rRNA, thus conferring antibiotic resistance against a number of macrolide antibiotics. The crystal structures of ErmC' and of its complexes with the cofactor S -adenosyl-l-methionine, the reaction product S-adenosyl-l-homocysteine and the methyltransferase inhibitor Sinefungin, respectively, show that the enzyme undergoes small conformational changes upon ligand binding. Overall, the ligand molecules bind to the protein in a similar mode as observed for other methyltransferases. Small differences between the binding of the amino acid parts of the different ligands are correlated with differences in their chemical structure. A model for the transition-state based on the atomic details of the active site is consistent with a one-step methyl-transfer mechanism and might serve as a first step towards the design of potent Erm inhibitors.

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / metabolism
  • Amino Acid Sequence
  • Antifungal Agents / metabolism
  • Bacillus subtilis / genetics
  • Binding Sites
  • Crystallography, X-Ray
  • Drug Resistance, Microbial
  • Ligands
  • Methyltransferases / chemistry*
  • Methyltransferases / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Protein Structure, Secondary
  • RNA, Ribosomal, 23S / biosynthesis
  • RNA, Ribosomal, 23S / metabolism
  • S-Adenosylhomocysteine / metabolism
  • S-Adenosylmethionine / metabolism


  • Antifungal Agents
  • Ligands
  • RNA, Ribosomal, 23S
  • S-Adenosylmethionine
  • S-Adenosylhomocysteine
  • Methyltransferases
  • rRNA (adenosine-O-2'-)methyltransferase
  • Adenosine
  • sinefungin

Associated data

  • PDB/1QAM
  • PDB/1QAN
  • PDB/1QAO
  • PDB/1QAQ