Mechanistic analysis of Riboswitch Ligand interactions provides insights into pharmacological control over gene expression.

ABSTRACT: Riboswitches are structured RNA elements that regulate gene expression upon binding to small molecule ligands. Understanding the mechanisms by which small molecules impact riboswitch activity is key to developing potent, selective ligands for these and other RNA targets. We report the structure-informed design of chemically diverse synthetic ligands for PreQ₁ riboswitches. Multiple X-ray co-crystal structures of synthetic ligands with the Thermoanaerobacter tengcongensis (Tte)-PreQ₁ riboswitch confirm a common binding site with the cognate ligand, despite considerable chemical differences among the ligands. Structure probing assays demonstrate that one ligand causes conformational changes similar to PreQ₁ in six structurally and mechanistically diverse PreQ

SUBMITTER: Parmar S 

PROVIDER: S-EPMC11408619 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature