6DN3

CRYSTAL STRUCTURE OF THE FMN RIBOSWITCH BOUND TO BRX1555 SPLIT RNA

Summary for 6DN3

• Entry DOI: 10.2210/pdb6dn3/pdb
• Descriptor: RNA RIBOSWITCH, RNA (56-MER), CHLORIDE ION, ... (7 entities in total)
• Functional Keywords: fmn, riboswitch, transcription, rna
• Biological source: Fusobacterium nucleatum; More
• Total number of polymer chains: 2
• Total formula weight: 36154.26

Authors

Vicens, Q.,Mondragon, E.,Reyes, F.E.,Berman, J.,Kaur, H.,Kells, K.,Wickens, P.,Wilson, J.,Gadwood, R.,Schostarez, H.,Suto, R.K.,Coish, P.,Blount, K.F.,Batey, R.T. (deposition date: 2018-06-05, release date: 2018-09-05, Last modification date: 2023-10-11)

Primary citation

Vicens, Q.,Mondragon, E.,Reyes, F.E.,Coish, P.,Aristoff, P.,Berman, J.,Kaur, H.,Kells, K.W.,Wickens, P.,Wilson, J.,Gadwood, R.C.,Schostarez, H.J.,Suto, R.K.,Blount, K.F.,Batey, R.T.
Structure-Activity Relationship of Flavin Analogues That Target the Flavin Mononucleotide Riboswitch.
ACS Chem. Biol., 13:2908-2919, 2018

PubMed Abstract: The flavin mononucleotide (FMN) riboswitch is an emerging target for the development of novel RNA-targeting antibiotics. We previously discovered an FMN derivative, 5FDQD, that protects mice against diarrhea-causing Clostridium difficile bacteria. Here, we present the structure-based drug design strategy that led to the discovery of this fluoro-phenyl derivative with antibacterial properties. This approach involved the following stages: (1) structural analysis of all available free and bound FMN riboswitch structures; (2) design, synthesis, and purification of derivatives; (3) in vitro testing for productive binding using two chemical probing methods; (4) in vitro transcription termination assays; and (5) resolution of the crystal structures of the FMN riboswitch in complex with the most mature candidates. In the process, we delineated principles for productive binding to this riboswitch, thereby demonstrating the effectiveness of a coordinated structure-guided approach to designing drugs against RNA.

PubMed: 30107111
DOI: 10.1021/acschembio.8b00533

Experimental method

X-RAY DIFFRACTION (2.8 Å)