8Q6N
Xanthin riboswitch in complex with oxypurinol
Summary for 8Q6N
| Entry DOI | 10.2210/pdb8q6n/pdb |
| Related | 7elr |
| Descriptor | Xanthin riboswitch NMT-46 (46-MER), Oxypurinol (3 entities in total) |
| Functional Keywords | rna riboswitch xanthin ligand, rna |
| Biological source | Ideonella sp. B508-1 |
| Total number of polymer chains | 1 |
| Total formula weight | 15056.07 |
| Authors | |
| Primary citation | Hedwig, V.,Sporing, M.,Ottlinger, J.,Kose, S.,Nar, H.,Schnapp, G.,Gottschling, D.,Klein, H.,Aspnes, G.,Klugmann, M.,Hartig, J.S. Engineering oxypurinol-responsive riboswitches based on bacterial xanthine aptamers for gene expression control in mammalian cell culture. Nucleic Acids Res., 53:-, 2025 Cited by PubMed Abstract: Riboswitch-mediated control of gene expression without the interference of potentially immunogenic proteins is a promising approach for the development of tailor-made tools for biological research and the advancement of gene therapies. However, the current selection of applicable ligands for synthetic riboswitches is limited and strategies have mostly relied on de novo selection of aptamers. Here, we show that the bacterial xanthine I riboswitch aptamer recognizes oxypurinol, the active metabolite of the widely prescribed anti-gout drug allopurinol (Zyloprim®). We have characterized the aptamer/oxypurinol interaction and present a crystal structure of the oxypurinol-bound aptamer, revealing a binding mode similar to that of the cognate ligand xanthine. We then constructed artificial oxypurinol-responsive riboswitches that showed functionality in human cells. By optimizing splicing-based oxypurinol riboswitches using three different strategies, transgene expression could be induced by >100-fold. In summary, we have developed recombinant RNA switches enabling on-demand regulation of gene expression in response to an established and safe drug. PubMed: 40087885DOI: 10.1093/nar/gkae1189 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.63 Å) |
Structure validation
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