A Stably Protonated Adenine Nucleotide with a Highly Shifted pK_a Value Stabilizes the Tertiary Structure of a GTP-Binding RNA Aptamer

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• 作者：Antje C. Wolter ; A. Katharina Weickhmann ; Amir H. Nasiri ; Katharina Hantke ; Dr. Oliver Ohlenschl&auml ; ger ; Dr. Christoph H. Wunderlich ; Prof. Dr. Christoph Kreutz ; Dr. Elke Duchardt-Ferner and Prof. Dr. Jens Wö ; hnert
• 刊名：Angewandte Chemie International Edition
• 出版年：2017
• 出版时间：January 2, 2017
• 年：2017
• 卷：56
• 期：1
• 页码：401-404
• 全文大小：2302K
• ISSN：1521-3773

文摘

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 pK_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 pK_a value for the protonation of this A residue in the complex is shifted by more than 5 pH units compared to the pK_a for A nucleotides in single-stranded RNA. This is the largest pK_a shift for an A residue in structured nucleic acids reported so far, and similar in size to the largest pK_a shifts observed for amino acid side chains in proteins. Both RNA pre-folding and ligand binding contribute to the pK_a shift.