6YD6

SaFtsZ-UCM152 (comp.20)

6YD6 の概要

• エントリーDOI: 10.2210/pdb6yd6/pdb
• 分子名称: Cell division protein FtsZ, GUANOSINE-5'-DIPHOSPHATE, 2,6-bis(fluoranyl)-3-[[3-(trifluoromethyl)phenyl]methoxy]benzamide, ... (7 entities in total)
• 機能のキーワード: cell division protein, cell cycle
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32712.67

構造登録者

Fernandez-Tornero, C.,Ruiz, F.M.,Andreu, J.M. (登録日: 2020-03-20, 公開日: 2021-07-28, 最終更新日: 2024-01-24)

主引用文献

Huecas, S.,Araujo-Bazan, L.,Ruiz, F.M.,Ruiz-Avila, L.B.,Martinez, R.F.,Escobar-Pena, A.,Artola, M.,Vazquez-Villa, H.,Martin-Fontecha, M.,Fernandez-Tornero, C.,Lopez-Rodriguez, M.L.,Andreu, J.M.
Targeting the FtsZ Allosteric Binding Site with a Novel Fluorescence Polarization Screen, Cytological and Structural Approaches for Antibacterial Discovery.
J.Med.Chem., 64:5730-5745, 2021

PubMed Abstract: Bacterial resistance to antibiotics makes previously manageable infections again disabling and lethal, highlighting the need for new antibacterial strategies. In this regard, inhibition of the bacterial division process by targeting key protein FtsZ has been recognized as an attractive approach for discovering new antibiotics. Binding of small molecules to the cleft between the N-terminal guanosine triphosphate (GTP)-binding and the C-terminal subdomains allosterically impairs the FtsZ function, eventually inhibiting bacterial division. Nonetheless, the lack of appropriate chemical tools to develop a binding screen against this site has hampered the discovery of FtsZ antibacterial inhibitors. Herein, we describe the first competitive binding assay to identify FtsZ allosteric ligands interacting with the interdomain cleft, based on the use of specific high-affinity fluorescent probes. This novel assay, together with phenotypic profiling and X-ray crystallographic insights, enables the identification and characterization of FtsZ inhibitors of bacterial division aiming at the discovery of more effective antibacterials.

PubMed: 33908781
DOI: 10.1021/acs.jmedchem.0c02207

実験手法

X-RAY DIFFRACTION (1.7 Å)