DISTANT RIBOSE 2'-O-METHYLATION OF 23S rRNA HELIX 69 PRE-ORDERS THE CAPREOMYCIN DRUG BINDING POCKET AT THE RIBOSOME SUBUNIT INTERFACE.

ABSTRACT: Loss of ribosomal RNA (rRNA) modifications incorporated by the intrinsic methyltransferase TlyA results in reduced sensitivity to tuberactinomycin antibiotics such as capreomycin. However, the mechanism by which rRNA methylation alters drug binding, particularly at the distant but functionally more important site in 23S rRNA Helix 69 (H69), is currently unknown. We determined high-resolution cryo-electron microscopy structures of the Mycolicibacterium smegmatis 70S ribosome with or without the two ribose 2'-O-methyl modifications incorporated by TlyA. In the unmodified ribosome, the tip of H69 adopts a more compact conformation, positioning two key nucleotides (A2137 and C2138) such that interactions with capreomycin would be lost and the binding pocket partially occluded. In contra

SUBMITTER: Nandi S 

PROVIDER: S-EPMC11580936 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature