5C45

Selective Small Molecule Inhibition of the FMN Riboswitch

Summary for 5C45

• Entry DOI: 10.2210/pdb5c45/pdb
• Related: 2YIF
• Descriptor: FMN Riboswitch, POTASSIUM ION, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: rna, translation, rna-inhibitor complex, rna/inhibitor
• Biological source: Fusobacterium nucleatum; More
• Total number of polymer chains: 2
• Total formula weight: 36213.84

Authors

Fischmann, T.O. (deposition date: 2015-06-17, release date: 2015-10-07, Last modification date: 2023-10-25)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.93 Å)