A Stably Protonated Adenine Nucleotide with a Highly Shifted pKa Value Stabilizes the Tertiary Structure of a GTP-Binding RNA Aptamer.
A Stably Protonated Adenine Nucleotide with a Highly Shifted pKa Value Stabilizes the Tertiary Structure of a GTP-Binding RNA Aptamer.
复制标题
DOI:
10.1002/anie.201609184
复制
发表时间:
2017-01
影响因子:
--
通讯作者:
Antje C. Wolter;A. K. Weickhmann;Amir H. Nasiri;Katharina Hantke;O. Ohlenschläger;C. Wunderlich;C. Kreutz;E. Duchardt-Ferner;J. Wöhnert
中科院分区:
文献类型:
--
作者:
Antje C. Wolter;A. K. Weickhmann;Amir H. Nasiri;Katharina Hantke;O. Ohlenschläger;C. Wunderlich;C. Kreutz;E. Duchardt-Ferner;J. Wöhnert
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 pKa 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 pKa value for the protonation of this A residue in the complex is shifted by more than 5 pH units compared to the pKa for A nucleotides in single-stranded RNA. This is the largest pKa shift for an A residue in structured nucleic acids reported so far, and similar in size to the largest pKa shifts observed for amino acid side chains in proteins. Both RNA pre-folding and ligand binding contribute to the pKa shift.