Structure of the Ribosomal RNA Decoding Site Containing a Selenium‐Modified Responsive Fluorescent Ribonucleoside Probe

Abstract

Comprehensive understanding of the structure–function relationship of RNA both in real time and at atomic level will have a profound impact in advancing our understanding of RNA functions in biology. Here, we describe the first example of a multifunctional nucleoside probe, containing a conformation‐sensitive fluorophore and an anomalous X‐ray diffraction label (5‐selenophene uracil), which enables the correlation of RNA conformation and recognition under equilibrium and in 3D. The probe incorporated into the bacterial ribosomal RNA decoding site, fluorescently reports antibiotic binding and provides diffraction information in determining the structure without distorting native RNA fold. Further, by comparing solution binding data and crystal structure, we gained insight on how the probe senses ligand‐induced conformational change in RNA. Taken together, our nucleoside probe represents a new class of biophysical tool that would complement available tools for functional RNA investigations.

Overcoming Aminoglycoside Enzymatic Resistance: Design of Novel Antibiotics and Inhibitors

“…Structural studies of the interactions between aminoglycosides and the RNA or AMEs involved in their enzymatic inactivation have been performed to identify the molecular nature of these recognition processes. The 4,5 or 4,6-disubstituted aminoglycosides specifically bind to the A-site with several conserved contacts, the majority of them corresponding to the pseudo-disaccharide neamine [ 83 , 84 , 85 ]. The synthesis of hybrid (4,5/4,6-) aminoglycosides, based on the superimposition of crystallographic structures, originated a new family of 4,5,6-aminoglycoside derivatives with a better prognosis against AMEs than the corresponding natural antibiotics [ 86 ] ( Figure 7 ).…”

Seleno‐Michael Reaction of Stable Functionalised Alkyl Selenols: A Versatile Tool for the Synthesis of Acyclic and Cyclic Unsymmetrical Alkyl and Vinyl Selenides

“…Organoselenium compounds occupy a relevant position in chemical sciences, with broad application in organic synthesis, [1] materials science [2] and polymer chemistry. [3] In addition, selenium-containing organic molecules play an increasingly important role in biology and in medicinal chemistry, [4] since they possess antioxidant, [5] enzyme modulator, [6] anticancer, [7] and cells growth inhibitor [8] activities. Due to their unique properties, in the last decade organoselenides have attracted growing interest among organic chemists, biologists, and medicinal chemists.…”

Theoretical characterization of sulfur-to-selenium substitution in an emissive RNA alphabet: impact on H-bonding potential and photophysical properties

“…26,27 Furthermore, selenium is present in RNA natural posttranscriptional modifications 28 and has already been artificially introduced in nucleic acid bases, in place of an oxygen atom for solving the phase problem 29 , but also for changing their pairing specificity 30,31 Notably, these two effects have been combined in a recent study proposing a Se-based modification. 32 Figure 1. Structures of the natural (A/G/U/C), modeled fluorescent nucleobases ( ts A/ ts G/ ts C/ ts U) and the modeled size expanded non-natural nucleobases ( xts A/ xts G/ xts C/ xts U).…”