6yd5
SaFtsZ-UCM151 (comp. 18)
Structural highlights
FunctionFTSZ_STAA8 Essential cell division protein that forms a contractile ring structure (Z ring) at the future cell division site. The regulation of the ring assembly controls the timing and the location of cell division. One of the functions of the FtsZ ring is to recruit other cell division proteins to the septum to produce a new cell wall between the dividing cells. Binds GTP and shows GTPase activity.[HAMAP-Rule:MF_00909][1] Publication Abstract from PubMedBacterial 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. Targeting the FtsZ Allosteric Binding Site with a Novel Fluorescence Polarization Screen, Cytological and Structural Approaches for Antibacterial Discovery.,Huecas S, Araujo-Bazan L, Ruiz FM, Ruiz-Avila LB, Martinez RF, Escobar-Pena A, Artola M, Vazquez-Villa H, Martin-Fontecha M, Fernandez-Tornero C, Lopez-Rodriguez ML, Andreu JM J Med Chem. 2021 May 13;64(9):5730-5745. doi: 10.1021/acs.jmedchem.0c02207. Epub , 2021 Apr 28. PMID:33908781[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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