6UC7

Structure of guanine riboswitch bound to N2-acetyl guanine

6UC7 の概要

• エントリーDOI: 10.2210/pdb6uc7/pdb
• 関連するPDBエントリー: 6UBU
• 分子名称: guanine riboswitch, COBALT HEXAMMINE(III), N-(6-oxo-6,9-dihydro-3H-purin-2-yl)acetamide, ... (4 entities in total)
• 機能のキーワード: riboswitch aptamer, guanine purine nucleobase, n2-acetyl guanine, rna
• 由来する生物種: Bacillus subtilis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 22988.87

構造登録者

Matyjasik, M.M.,Batey, R.T. (登録日: 2019-09-15, 公開日: 2020-07-22, 最終更新日: 2023-10-11)

主引用文献

Matyjasik, M.M.,Hall, S.D.,Batey, R.T.
High Affinity Binding of N2-Modified Guanine Derivatives Significantly Disrupts the Ligand Binding Pocket of the Guanine Riboswitch.
Molecules, 25:-, 2020

PubMed Abstract: Riboswitches are important model systems for the development of approaches to search for RNA-targeting therapeutics. A principal challenge in finding compounds that target riboswitches is that the effector ligand is typically almost completely encapsulated by the RNA, which severely limits the chemical space that can be explored. Efforts to find compounds that bind the guanine/adenine class of riboswitches with a high affinity have in part focused on purines modified at the C6 and C2 positions. These studies have revealed compounds that have low to sub-micromolar affinity and, in a few cases, have antimicrobial activity. To further understand how these compounds interact with the guanine riboswitch, we have performed an integrated structural and functional analysis of representative guanine derivatives with modifications at the C8, C6 and C2 positions. Our data indicate that while modifications of guanine at the C6 position are generally unfavorable, modifications at the C8 and C2 positions yield compounds that rival guanine with respect to binding affinity. Surprisingly, C2-modified guanines such as 2-acetylguanine completely disrupt a key Watson-Crick pairing interaction between the ligand and RNA. These compounds, which also modulate transcriptional termination as efficiently as guanine, open up a significant new chemical space of guanine modifications in the search for antimicrobial agents that target purine riboswitches.

PubMed: 32414072
DOI: 10.3390/molecules25102295

実験手法

X-RAY DIFFRACTION (1.798 Å)