A Crystal Structure of a Functional RNA Molecule Containing an Artificial Nucleobase Pair |
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| Authors: | Zunyi Yang Dr. Sandip A. Shelke Dr. Julien Herrou Dr. Hyo‐Joong Kim Dr. Myong‐Jung Kim Prof. Joseph A. Piccirilli Prof. Steven A. Benner |
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| Affiliation: | 1. Foundation for Applied Molecular Evolution, Firebird Biomolecular Sciences LLC, 13709 Progress Boulevard, Alachua, FL 32615 (USA);2. Department of Biochemistry and Molecular Biology, Department of Chemistry, University of Chicago, Chicago, IL 60637 (USA) |
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| Abstract: | As one of its goals, synthetic biology seeks to increase the number of building blocks in nucleic acids. While efforts towards this goal are well advanced for DNA, they have hardly begun for RNA. Herein, we present a crystal structure for an RNA riboswitch where a stem C:G pair has been replaced by a pair between two components of an artificially expanded genetic‐information system (AEGIS), Z and P , (6‐amino‐5‐nitro‐2(1H)‐pyridone and 2‐amino‐imidazo[1,2‐a]‐1,3,5‐triazin‐4‐(8H)‐one). The structure shows that the Z : P pair does not greatly change the conformation of the RNA molecule nor the details of its interaction with a hypoxanthine ligand. This was confirmed in solution by in‐line probing, which also measured a 3.7 nM affinity of the riboswitch for guanine. These data show that the Z : P pair mimics the natural Watson–Crick geometry in RNA in the first example of a crystal structure of an RNA molecule that contains an orthogonal added nucleobase pair. |
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| Keywords: | crystal structure expanded DNA in‐line probing riboswitch synthetic biology |
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