Login / Signup

Structure-based characterization and compound identification of the wild-type THF class-II riboswitch.

Chunyan LiXiaochen XuZhi GengLuqian ZhengQianqian SongXin ShenJingjing WuJin ZhaoHongcheng LiMengqi HeXiaoqing TaiJisheng LiuJinbiao MaYuhui DongAiming Ren
Published in: Nucleic acids research (2024)
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.
Keyphrases
  • wild type
  • drug discovery
  • ms ms
  • nucleic acid
  • healthcare
  • bioinformatics analysis
  • gene expression
  • genome wide
  • social media
  • molecular docking
  • molecular dynamics simulations
  • dna binding
  • health information