9V4V

Crystal structure of Guanine-II riboswitch in complex with isoxanthopterin

Summary for 9V4V

• Entry DOI: 10.2210/pdb9v4v/pdb
• Descriptor: RNA (71-MER), 2-aminopteridine-4,7(3H,8H)-dione, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: guanine riboswitch, rna
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 1
• Total formula weight: 23165.93

Authors

Li, H.C.,Ren, A.M. (deposition date: 2025-05-24, release date: 2025-11-26)

Primary citation

Li, H.,Shen, X.,Xu, X.,Tai, X.,He, M.,Zhang, J.,Ren, A.
Ligand specificity and adaptability revealed by the first Guanine-II riboswitch tertiary structure.
Nucleic Acids Res., 53:-, 2025

PubMed Abstract: A comprehensive understanding of the fundamental principles governing RNA-small molecule interactions is crucial for advancing RNA-targeting therapeutics with small molecules. Riboswitches, a class of noncoding RNAs, regulate gene expression by direct interaction with small-molecule metabolites. In this work, we report an in-depth structure-based investigation of a newly identified riboswitch, Guanine-II, which, despite sharing a conserved scaffold with the Guanine-I riboswitch, exhibits strikingly distinct small molecule ligand-binding characteristics. Through a comprehensive structural analysis of the Guanine-II riboswitch bound to various guanine analogs, combined with comparative studies of other guanine riboswitch variants, including Guanine-I and Xanthine-II riboswitches, as well as isothermal titration calorimetry, we reveal local structural rearrangements that precisely modulate small-molecule ligand adaptability. We further demonstrate that subtle differences in the composition and peripheral architecture of the binding pocket are key determinants of ligand-binding specificity. Additionally, based on the similarity in ligand recognition patterns with the tetrahydrofolate-II riboswitch, we identified additional compounds that bind to the Guanine-II riboswitch through a structure-guided rational search, providing valuable structural insights for the discovery of small molecules targeting RNA.

PubMed: 40966503
DOI: 10.1093/nar/gkaf884

Experimental method

X-RAY DIFFRACTION (3.12 Å)