6wzr

Fusibacterium ulcerans ZTP riboswitch bound to p-1-pyridinyl AICA

spinqualitylabelsall models 6wzr, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6wzr is a 2 chain structure with sequence from Fusobacterium ulcerans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.2Å Ligands: K, MG, UG1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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 approximately 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. Parallel Discovery Strategies Provide a Basis for Riboswitch Ligand Design.,Tran B, Pichling P, Tenney L, Connelly CM, Moon MH, Ferre-D'Amare AR, Schneekloth JS Jr, Jones CP Cell Chem Biol. 2020 Oct 15;27(10):1241-1249.e4. doi:, 10.1016/j.chembiol.2020.07.021. Epub 2020 Aug 13. PMID:32795418 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Riboswitch 3D structures

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