THE STRUCTURE OF THE RRNA METHYLTRANSFERASE ERMC': IMPLICATIONS FOR THE REACTION MECHANISM
Classification:
TRANSFERASE
Technique:
X-Ray Diffraction
Resolution:
2.2
R value free:
0.251
R value observed:
R value work:
0.221
Abstract of the PDB Structure's related Publication:
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.
ErmC' methylates the exocyclic amine of A2058 (E. coli numbering) in helix 75 of 23S rRNA. It is responsible for the development of bacterial resistance to lincosamide/streptogramin-type of antibiotics.
Alanine-scanning mutagenesis of the predicted rRNA-binding domain of ErmC' redefines the substrate-binding site and suggests a model for protein-RNA interactions.
Maravic G, Bujnicki JM, Feder M, Pongor S, Flogel M
Alanine-scanning mutagenesis of the predicted rRNA-binding domain of ErmC' redefines the substrate-binding site and suggests a model for protein-RNA interactions.
Crystal structure of ErmC', an rRNA methyltransferase which mediates antibiotic resistance in bacteria.
Family background of children with Down's syndrome and of children with a similar degree of mental retardation.
Sequence and properties of pIM13, a macrolide-lincosamide-streptogramin B resistance plasmid from Bacillus subtilis.
Substrate requirements for ErmC' methyltransferase activity.
The 2.2 A structure of the rRNA methyltransferase ErmC' and its complexes with cofactor and cofactor analogs: implications for the reaction mechanism.