RT Journal Article
T1 Targeting the FtsZ Allosteric Binding Site with a Novel Fluorescence Polarization Screen, Cytological and Structural Approaches for Antibacterial Discovery
A1 Huecas, Sonia
A1 Araujo Bazán, Lidia
A1 Ruiz, Federico
A1 Ruiz Ávila, Laura
A1 Martínez, R. Fernando
A1 Escobar Peña, Ana Andrea
A1 Artola, Marta
A1 Vázquez Villa, María Del Henar
A1 Martín-Fontecha Corrales, María Del Mar
A1 Fernández Tornero, Carlos
A1 López Rodríguez, María Luz
A1 Andreu, José M.
AB 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.
PB ACS Publications
SN 0022-2623
YR 2021
FD 2021-04-28
LK https://hdl.handle.net/20.500.14352/8590
UL https://hdl.handle.net/20.500.14352/8590
LA eng
NO Sonia Huecas, Lidia Araújo-Bazán, Federico M. Ruiz, Laura B. Ruiz-Ávila, R. Fernando Martínez, Andrea Escobar-Peña, Marta Artola, Henar Vázquez-Villa, Mar Martín-Fontecha, Carlos Fernández-Tornero, María L. López-Rodríguez, and José M. Andreu Journal of Medicinal Chemistry 2021 64 (9), 5730-5745 DOI: 10.1021/acs.jmedchem.0c02207
NO CRUE-CSIC (Acuerdos Transformativos 2021)Received: December 21, 2020Published: April 28, 2021
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Ministerio de Educación, Ciencia y Deporte de España
DS Docta Complutense
RD 20 abr 2025