6WZR
Fusibacterium ulcerans ZTP riboswitch bound to p-1-pyridinyl AICA
Summary for 6WZR
| Entry DOI | 10.2210/pdb6wzr/pdb |
| Descriptor | Fusibacterium ulcerans ZTP riboswitch, MAGNESIUM ION, POTASSIUM ION, ... (5 entities in total) |
| Functional Keywords | riboswitch, pseudoknot, purine biosynthesis, aicar, rna |
| Biological source | Fusobacterium ulcerans |
| Total number of polymer chains | 2 |
| Total formula weight | 49045.37 |
| Authors | Pichling, P.,Jones, C.P.,Ferre-D'Amare, A.R.,Tran, B. (deposition date: 2020-05-14, release date: 2021-03-24, Last modification date: 2023-10-18) |
| Primary citation | Tran, B.,Pichling, P.,Tenney, L.,Connelly, C.M.,Moon, M.H.,Ferre-D'Amare, A.R.,Schneekloth Jr., J.S.,Jones, C.P. Parallel Discovery Strategies Provide a Basis for Riboswitch Ligand Design. Cell Chem Biol, 27:1241-1249.e4, 2020 Cited by PubMed Abstract: Riboswitches are mRNA domains that make gene-regulatory decisions upon binding their cognate ligands. Bacterial riboswitches that specifically recognize 5-aminoimidazole-4-carboxamide riboside 5'-monophosphate (ZMP) and 5'-triphosphate (ZTP) regulate genes involved in folate and purine metabolism. Now, we have developed synthetic ligands targeting ZTP riboswitches by replacing the sugar-phosphate moiety of ZMP with various functional groups, including simple heterocycles. Despite losing hydrogen bonds from ZMP, these analogs bind ZTP riboswitches with similar affinities as the natural ligand, and activate transcription more strongly than ZMP in vitro. The most active ligand stimulates gene expression ∼3 times more than ZMP in a live Escherichia coli reporter. Co-crystal structures of the Fusobacterium ulcerans ZTP riboswitch bound to synthetic ligands suggest stacking of their pyridine moieties on a conserved RNA nucleobase primarily determines their higher activity. Altogether, these findings guide future design of improved riboswitch activators and yield insights into how RNA-targeted ligand discovery may proceed. PubMed: 32795418DOI: 10.1016/j.chembiol.2020.07.021 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.2 Å) |
Structure validation
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