6DN2

CRYSTAL STRUCTURE OF THE FMN RIBOSWITCH BOUND TO BRX1354 SPLIT RNA

6DN2 の概要

• エントリーDOI: 10.2210/pdb6dn2/pdb
• 分子名称: RNA RIBOSWITCH, RNA (56-MER), MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: fmn, riboswitch, transcription, rna
• 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: 36194.60

構造登録者

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. (登録日: 2018-06-05, 公開日: 2018-09-05, 最終更新日: 2023-10-11)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.88 Å)