5KX9

Selective Small Molecule Inhibition of the FMN Riboswitch

Summary for 5KX9

• Entry DOI: 10.2210/pdb5kx9/pdb
• 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: 36302.53

Authors

Fischmann, T.O. (deposition date: 2016-07-20, release date: 2016-08-24, Last modification date: 2023-10-25)

Primary citation

Howe, J.A.,Xiao, L.,Fischmann, T.O.,Wang, H.,Tang, H.,Villafania, A.,Zhang, R.,Barbieri, C.M.,Roemer, T.
Atomic resolution mechanistic studies of ribocil: A highly selective unnatural ligand mimic of the E. coli FMN riboswitch.
Rna Biol., 13:946-954, 2016

PubMed Abstract: Bacterial riboswitches are non-coding RNA structural elements that direct gene expression in numerous metabolic pathways. The key regulatory roles of riboswitches, and the urgent need for new classes of antibiotics to treat multi-drug resistant bacteria, has led to efforts to develop small-molecules that mimic natural riboswitch ligands to inhibit metabolic pathways and bacterial growth. Recently, we reported the results of a phenotypic screen targeting the riboflavin biosynthesis pathway in the Gram-negative bacteria Escherichia coli that led to the identification of ribocil, a small molecule inhibitor of the flavin mononucleotide (FMN) riboswitch controlling expression of this biosynthetic pathway. Although ribocil is structurally distinct from FMN, ribocil functions as a potent and highly selective synthetic mimic of the natural ligand to repress riboswitch-mediated ribB gene expression and inhibit bacterial growth both in vitro and in vivo. Herein, we expand our analysis of ribocil; including mode of binding in the FMN binding pocket of the riboswitch, mechanisms of resistance and structure-activity relationship guided efforts to generate more potent analogs.

PubMed: 27485612
DOI: 10.1080/15476286.2016.1216304

Experimental method

X-RAY DIFFRACTION (2.9 Å)