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http://hdl.handle.net/10662/21891
Title: | Targeting the FtsZ allosteric binding site with a novel fluorescence polarization screen, cytological and structural approaches for antibacterial discovery |
Authors: | Huecas, Sonia Araújo Bazán, Lidia Ruiz, Federico M. Ruiz Ávila, Laura B. Martínez Vázquez, Rafael Fernando Escobar Peña, Andrea Artola, Marta Vázquez Villa, Henar Martín Fontecha, Mar Fernández Tornero, Carlos López Rodríguez, María L. Andreu, José M. |
Keywords: | Fluorescence;Inhibitors;Probes;Fluorescencia;Inhibidores;Sondas;Magnetic properties;Propiedades magnéticas;Screening assays;Ensayos de detección |
Issue Date: | 2021-01-03 |
Publisher: | ACS Publications |
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. |
URI: | http://hdl.handle.net/10662/21891 |
ISSN: | 0022-2623 |
DOI: | 10.1021/acs.jmedchem.0c02207 |
Appears in Collections: | DQOIN - Artículos |
Files in This Item:
File | Description | Size | Format | |
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acs_jmedchem_0c02207.pdf | 4,82 MB | Adobe PDF | View/Open |
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