Synthetic ligands for PreQ₁ riboswitches provide structural and mechanistic insights into targeting RNA tertiary structure.

ABSTRACT: Riboswitches are naturally occurring RNA aptamers that regulate gene expression by binding to specific small molecules. Riboswitches control the expression of essential bacterial genes and are important models for RNA-small molecule recognition. Here, we report the discovery of a class of synthetic small molecules that bind to PreQ₁ riboswitch aptamers. These molecules bind specifically and reversibly to the aptamers with high affinity and induce a conformational change. Furthermore, the ligands modulate riboswitch activity through transcriptional termination despite no obvious chemical similarity to the cognate ligand. X-ray crystallographic studies reveal that the ligands share a binding site with the cognate ligand but make different contacts. Finally, alteration of the chemi

SUBMITTER: Connelly CM 

PROVIDER: S-EPMC6445138 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature