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A Crystal Structure of a Functional RNA Molecule Containing an Artificial Nucleobase Pair
Author(s) -
Hernandez Armando R.,
Shao Yaming,
Hoshika Shuichi,
Yang Zunyi,
Shelke Sandip A.,
Herrou Julien,
Kim HyoJoong,
Kim MyongJung,
Piccirilli Joseph A.,
Benner Steven A.
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201504731
Subject(s) - nucleobase , riboswitch , rna , guanine , nucleic acid , nucleic acid structure , dna , crystal structure , chemistry , molecule , molecular structure of nucleic acids: a structure for deoxyribose nucleic acid , nucleotide , stereochemistry , crystallography , base pair , non coding rna , biochemistry , gene , organic chemistry
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 Herein, we present a crystal structure for an RNA riboswitch where a stem C:G pair has been replaced by a pair between two components of an artificially expanded genetic‐information system (AEGIS), Z and P , (6‐amino‐5‐nitro‐2(1 H )‐pyridone and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 n M 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.