A Crystal Structure of a Functional RNA Molecule Containing an Artificial Nucleobase Pair. (16th July 2015)

• Record Type: Journal Article
• Authors: Hernandez, Armando R.; Shao, Yaming; Hoshika, Shuichi; Yang, Zunyi; Shelke, Sandip A.; Herrou, Julien; Kim, Hyo‐Joong; Kim, Myong‐Jung; Piccirilli, Joseph A.; Benner, Steven A.
• Is Part Of: Angewandte Chemie. Volume 127:Number 34(2015)
• Page Start: 9991
• Page End: 9994
• Publication Date: 2015-07-16
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201504731
• Languages: English
• ISSNs: 0044-8249

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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 Herein, we present a crystal structure for an RNA riboswitch where a stem C:G pair has been replaced by a pair between two components of an artificially expanded genetic‐information system (AEGIS), <bold>Z</bold> and <bold>P</bold>, (6‐amino‐5‐nitro‐2(1<italic>H</italic>)‐pyridone and 2‐amino‐imidazo[1, 2‐a]‐1, 3, 5‐triazin‐4‐(8<italic>H</italic>)‐one). The structure shows that the <bold>Z</bold>:<bold>P</bold> 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 n<sc>M</sc> affinity of the riboswitch for guanine. These data show that the <bold>Z</bold>:<bold>P</bold> 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.</p> </abstract>