5C45

Selective Small Molecule Inhibition of the FMN Riboswitch

5C45 の概要

• エントリーDOI: 10.2210/pdb5c45/pdb
• 関連するPDBエントリー: 2YIF
• 分子名称: FMN Riboswitch, POTASSIUM ION, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: rna, translation, rna-inhibitor complex, rna/inhibitor
• 由来する生物種: Fusobacterium nucleatum; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36213.84

構造登録者

Fischmann, T.O. (登録日: 2015-06-17, 公開日: 2015-10-07, 最終更新日: 2023-10-25)

主引用文献

Howe, J.A.,Wang, H.,Fischmann, T.O.,Balibar, C.J.,Xiao, L.,Galgoci, A.M.,Malinverni, J.C.,Mayhood, T.,Villafania, A.,Nahvi, A.,Murgolo, N.,Barbieri, C.M.,Mann, P.A.,Carr, D.,Xia, E.,Zuck, P.,Riley, D.,Painter, R.E.,Walker, S.S.,Sherborne, B.,de Jesus, R.,Pan, W.,Plotkin, M.A.,Wu, J.,Rindgen, D.,Cummings, J.,Garlisi, C.G.,Zhang, R.,Sheth, P.R.,Gill, C.J.,Tang, H.,Roemer, T.
Selective small-molecule inhibition of an RNA structural element.
Nature, 526:672-677, 2015

PubMed Abstract: Riboswitches are non-coding RNA structures located in messenger RNAs that bind endogenous ligands, such as a specific metabolite or ion, to regulate gene expression. As such, riboswitches serve as a novel, yet largely unexploited, class of emerging drug targets. Demonstrating this potential, however, has proven difficult and is restricted to structurally similar antimetabolites and semi-synthetic analogues of their cognate ligand, thus greatly restricting the chemical space and selectivity sought for such inhibitors. Here we report the discovery and characterization of ribocil, a highly selective chemical modulator of bacterial riboflavin riboswitches, which was identified in a phenotypic screen and acts as a structurally distinct synthetic mimic of the natural ligand, flavin mononucleotide, to repress riboswitch-mediated ribB gene expression and inhibit bacterial cell growth. Our findings indicate that non-coding RNA structural elements may be more broadly targeted by synthetic small molecules than previously expected.

PubMed: 26416753
DOI: 10.1038/nature15542

実験手法

X-RAY DIFFRACTION (2.93 Å)