DSSR-PyMOL cartoon-block schematics: PDB entry 8xzr

PDB-id

8xzr; DSSR-derived features in text and JSON formats

Class

RNA

Method

X-ray (1.83 Å)

Summary

Crystal structure of fole riboswitch with 8-nh2 guanine

Reference

Li C, Xu X, Geng Z, Zheng L, Song Q, Shen X, Wu J, Zhao J, Li H, He M, Tai X, Zhang L, Ma J, Dong Y, Ren A (2024): "Structure-based characterization and compound identification of the wild-type THF class-II riboswitch." Nucleic Acids Res., 52, 8454-8465. doi: 10.1093/nar/gkae377.

Abstract

Riboswitches are conserved regulatory RNA elements participating in various metabolic pathways. Recently, a novel RNA motif known as the folE RNA motif was discovered upstream of folE genes. It specifically senses tetrahydrofolate (THF) and is therefore termed THF-II riboswitch. To unravel the ligand recognition mechanism of this newly discovered riboswitch and decipher the underlying principles governing its tertiary folding, we determined both the free-form and bound-form THF-II riboswitch in the wild-type sequences. Combining structural information and isothermal titration calorimetry (ITC) binding assays on structure-based mutants, we successfully elucidated the significant long-range interactions governing the function of THF-II riboswitch and identified additional compounds, including alternative natural metabolites and potential lead compounds for drug discovery, that interact with THF-II riboswitch. Our structural research on the ligand recognition mechanism of the THF-II riboswitch not only paves the way for identification of compounds targeting riboswitches, but also facilitates the exploration of THF analogs in diverse biological contexts or for therapeutic applications.