6VZC

Tandem UU:GA mismatch within an RNA helix

6VZC の概要

• エントリーDOI: 10.2210/pdb6vzc/pdb
• NMR情報: BMRB: 30730
• 分子名称: RNA 28-mer (1 entity in total)
• 機能のキーワード: mismatch, internal loop, structural motif, ga base pair, uu base pair, rna
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 8963.33

構造登録者

Nikonowicz, E.P.,Chang, A.T. (登録日: 2020-02-28, 公開日: 2020-09-02, 最終更新日: 2024-05-15)

主引用文献

Chang, A.T.,Chen, L.,Song, L.,Zhang, S.,Nikonowicz, E.P.
2-Amino-1,3-benzothiazole-6-carboxamide Preferentially Binds the Tandem Mismatch Motif r(UY:GA).
Biochemistry, 59:3225-3234, 2020

PubMed Abstract: RNA helices are often punctuated with non-Watson-Crick features that may be targeted by chemical compounds, but progress toward identifying such compounds has been slow. We embedded a tandem UU:GA mismatch motif (5'-UG-3':5'-AU-3') within an RNA hairpin stem to identify compounds that bind the motif specifically. The three-dimensional structure of the RNA hairpin and its interaction with a small molecule identified through virtual screening are presented. The G-A mismatch forms a sheared pair upon which the U-U base pair stacks. The hydrogen bond configuration of the U-U pair involves O2 of the U adjacent to the G and O4 of the U adjacent to the A. The G-A and U-U pairs are flanked by A-U and G-C base pairs, respectively, and the stability of the mismatch is greater than when the motif is within the context of other flanking base pairs or when the 5'-3' orientation of the G-A and U-U pairs is swapped. Residual dipolar coupling constants were used to generate an ensemble of structures against which a virtual screen of 64480 small molecules was performed. The tandem mismatch was found to be specific for one compound, 2-amino-1,3-benzothiazole-6-carboxamide, which binds with moderate affinity but extends the motif to include the flanking A-U and G-C base pairs. The finding that the affinity for the UU:GA mismatch is dependent on flanking sequence emphasizes the importance of the motif context and potentially increases the number of small noncanonical features within RNA that can be specifically targeted by small molecules.

PubMed: 32786414
DOI: 10.1021/acs.biochem.0c00369

実験手法

SOLUTION NMR