Download MendeleyStructure-based characterization and compound identification of the wild-type THF class-II riboswitch.
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) Nucleic Acids Res 52: 8454-8465
- PubMed: 38769061
- DOI: https://doi.org/10.1093/nar/gkae377
- Primary Citation of Related Structures:
8XZE, 8XZK, 8XZL, 8XZM, 8XZN, 8XZO, 8XZP, 8XZQ, 8XZR, 8XZW - PubMed 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.
Organizational Affiliation:
Life Sciences Institute, Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang Key Laboratory of Biotherapy, Zhejiang University, Hangzhou?310058, China.
