A Crystal Structure of a Functional RNA Molecule Containing an Artificial Nucleobase Pair. Issue 34 (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 international edition. Volume 54:Issue 34(2015)
• Page Start: 9853
• Page End: 9856
• Publication Date: 2015-07-16
• Subjects: crystal structure -- expanded DNA -- in‐line probing -- riboswitch -- synthetic biology; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201504731
• Languages: English
• ISSNs: 1433-7851

Abstract

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 Herein, we present a crystal structure for an RNA riboswitch where a stem C:G pair has been replaced by a pair between two components of an artificially expanded genetic‐information system (AEGIS), Z and P, (6‐amino‐5‐nitro‐2(1 H )‐pyridone and 2‐amino‐imidazo[1, 2‐a]‐1, 3, 5‐triazin‐4‐(8 H )‐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. Abstract : ZiP fasteners : On replacing C:G base with the artificial Z:P pair (blue) a crystal structure (see picture) of the guanosine riboswitch (purple), bound to a hypoxanthine ligand (red), is obtained which can be superimposed on the structure of the native form (green). This is the first crystal structure of an RNA molecule built from a six‐nucleotide artificially expanded genetic‐information system.