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A riboswitch is an element of an RNA molecule, typically found in the 5’- untranslated region, which controls gene expression via binding interactions with a ligand. Many classes of riboswitches exist which bind different ligands, and each class does so with high specificity, acting as a natural sensor of metabolites or small-metal ions. Upon binding to the target ligand, the riboswitch undergoes a structural change that will either allow the downstream gene to be expressed (upregulation), or prevent expression from occurring (downregulation). The pbuX-xpt riboswitch is a purine-class riboswitch that naturally binds to guanine. Because this riboswitch plays a role in the biosynthesis of a key cellular metabolite, current research efforts have been devoted to assessing the riboswitch as a potential antibiotic drug target. Our efforts have been concentrated in the development, and subsequent assaying of purine analogues, or molecules that resemble guanine (the natural ligand) and guanosine in structure, albeit with modifications at the C2 and C6 positions. Through the use of an in-vivo β-Galactosidase assay and in-vitro structural probing, we hope to elucidate the inhibitory potential, and the binding affinity of each ligand on the riboswitch.
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McDonough, Brian, "On the Use of Nucleosides as Ligand Analogues in Interactions with the pbuX-xpt Purine Riboswitch" (2015). Senior Projects Spring 2015. 284.