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Publication Abstract from PubMed

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.

Structure-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 Nucleic Acids Res. 2024 May 20:gkae377. doi: 10.1093/nar/gkae377. PMID:38769061^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.