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Your search keyword '"Lopez-Rodriguez, M.L. [0000-0001-8607-1085]"' showing total 2 results
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2 results on '"Lopez-Rodriguez, M.L. [0000-0001-8607-1085]"'

1. Targeting the FtsZ allosteric binding site with a novel fluorescence polarization screen, cytological and structural approaches for antibacterial discovery

Author

Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Huecas, Sonia [0000-0002-6419-441X], Araújo-Bazán, Lidia [0000-0002-8750-7706], Ruiz, Federico M. [0000-0002-0385-7777], Martínez, R. Fernando [0000-0002-3278-6074], Artola, M. [0000-0002-3051-3902], Vazquez-Villa, Henar [0000-0001-7911-3160], Martin-Fontecha, M. [0000-0002-4848-0109], Fernández-Tornero, Carlos [0000-0001-5097-731X], Lopez-Rodriguez, M.L. [0000-0001-8607-1085], Andreu, José Manuel [0000-0001-8064-6933], Huecas, Sonia, Araújo-Bazán, Lidia, Ruiz, Federico M., Ruiz-Avila, Laura B., Martínez, R. Fernando, Escobar-Peña, Andrea, Artola, Marta, Vazquez-Villa, Henar, Martín-Fontecha, Mar, Fernández-Tornero, Carlos, Lopez-Rodriguez, M.L., Andreu, José Manuel, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Huecas, Sonia [0000-0002-6419-441X], Araújo-Bazán, Lidia [0000-0002-8750-7706], Ruiz, Federico M. [0000-0002-0385-7777], Martínez, R. Fernando [0000-0002-3278-6074], Artola, M. [0000-0002-3051-3902], Vazquez-Villa, Henar [0000-0001-7911-3160], Martin-Fontecha, M. [0000-0002-4848-0109], Fernández-Tornero, Carlos [0000-0001-5097-731X], Lopez-Rodriguez, M.L. [0000-0001-8607-1085], Andreu, José Manuel [0000-0001-8064-6933], Huecas, Sonia, Araújo-Bazán, Lidia, Ruiz, Federico M., Ruiz-Avila, Laura B., Martínez, R. Fernando, Escobar-Peña, Andrea, Artola, Marta, Vazquez-Villa, Henar, Martín-Fontecha, Mar, Fernández-Tornero, Carlos, Lopez-Rodriguez, M.L., and Andreu, José Manuel

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.

Published
2021

2. Targeting the FtsZ Allosteric Binding Site with a Novel Fluorescence Polarization Screen, Cytological and Structural Approaches for Antibacterial Discovery

Author

Federico M. Ruiz, Andrea Escobar-Peña, María L. López-Rodríguez, José Manuel Andreu, Mar Martín-Fontecha, Sonia Huecas, Marta Artola, Henar Vázquez-Villa, Laura B. Ruiz-Avila, Lidia Araújo-Bazán, R Fernando Martínez, Carlos Fernández-Tornero, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Huecas, Sonia [0000-0002-6419-441X], Araújo-Bazán, Lidia [0000-0002-8750-7706], Ruiz, Federico M. [0000-0002-0385-7777], Martínez, R. Fernando [0000-0002-3278-6074], Artola, M. [0000-0002-3051-3902], Vazquez-Villa, Henar [0000-0001-7911-3160], Martin-Fontecha, M. [0000-0002-4848-0109], Fernández-Tornero, Carlos [0000-0001-5097-731X], Lopez-Rodriguez, M.L. [0000-0001-8607-1085], Andreu, José Manuel [0000-0001-8064-6933], Huecas, Sonia, Araújo-Bazán, Lidia, Ruiz, Federico M., Martínez, R. Fernando, Artola, M., Vazquez-Villa, Henar, Martin-Fontecha, M., Fernández-Tornero, Carlos, Lopez-Rodriguez, M.L., and Andreu, José Manuel

Subjects
Staphylococcus aureus, GTP', Pyridines, Allosteric regulation, Fluorescence Polarization, Computational biology, Microbial Sensitivity Tests, Guanosine triphosphate, Crystallography, X-Ray, Ligands, 01 natural sciences, Fluorescence, Article, Small Molecule Libraries, 03 medical and health sciences, chemistry.chemical_compound, Structure-Activity Relationship, Bacterial Proteins, Drug Discovery, Magnetic properties, FtsZ, 030304 developmental biology, Fluorescent Dyes, 0303 health sciences, biology, Chemistry, Inhibitors, Química orgánica, Phenotype, Small molecule, Screening assays, 0104 chemical sciences, Anti-Bacterial Agents, 010404 medicinal & biomolecular chemistry, Cytoskeletal Proteins, Benzamides, biology.protein, Molecular Medicine, Probes, Fluorescence anisotropy, Function (biology), Allosteric Site, Bacillus subtilis, Protein Binding
Abstract

51 p.-6 fig.-1 tab.-4 schem.-1 graph. abst., 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., Thiswork was supported by grants BFU 2014-51823-R (J.M.A.),SAF2016-78792-R, PID2019-106279RB-I00 (M.L.L.-R.), BFU2017-87387-P (C.F.-T.), and predoctoral FPU fellowshipsfrom MECD (A.E.-P. and M.A.).

Published
2021

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