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A Stably Protonated Adenine Nucleotide with a Highly Shifted p K a Value Stabilizes the Tertiary Structure of a GTP‐Binding RNA Aptamer
Author(s) -
Wolter Antje C.,
Weickhmann A. Katharina,
Nasiri Amir H.,
Hantke Katharina,
Ohlenschläger Oliver,
Wunderlich Christoph H.,
Kreutz Christoph,
DuchardtFerner Elke,
Wöhnert Jens
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201609184
Subject(s) - protonation , rna , nucleotide , gtp' , chemistry , aptamer , nucleic acid , nucleic acid structure , stereochemistry , protein tertiary structure , hydrogen bond , base pair , crystallography , residue (chemistry) , riboswitch , binding site , molecule , biochemistry , dna , enzyme , biology , non coding rna , organic chemistry , ion , genetics , gene
RNA tertiary structure motifs are stabilized by a wide variety of hydrogen‐bonding interactions. Protonated A and C nucleotides are normally not considered to be suitable building blocks for such motifs since their p K a values are far from physiological pH. Here, we report the NMR solution structure of an in vitro selected GTP‐binding RNA aptamer bound to GTP with an intricate tertiary structure. It contains a novel kind of base quartet stabilized by a protonated A residue. Owing to its unique structural environment in the base quartet, the p K a value for the protonation of this A residue in the complex is shifted by more than 5 pH units compared to the p K a for A nucleotides in single‐stranded RNA. This is the largest p K a shift for an A residue in structured nucleic acids reported so far, and similar in size to the largest p K a shifts observed for amino acid side chains in proteins. Both RNA pre‐folding and ligand binding contribute to the p K a shift.