6si9

FtsZ-refold

spinqualitylabelsall models 6si9, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6si9 is a 1 chain structure with sequence from Staphylococcus aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: CA, EDO, GDP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FTSZ_STAAU 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] Publication Abstract from PubMed The essential bacterial division protein FtsZ uses GTP binding and hydrolysis to assemble into dynamic filaments that treadmill around the Z-ring, guiding septal wall synthesis and cell division. FtsZ is a structural homolog of tubulin and a target for discovering new antibiotics. Here, using FtsZ from the pathogen S aureus (SaFtsZ), we reveal that, prior to assembly, FtsZ monomers require nucleotide binding for folding; this is possibly relevant to other mesophilic FtsZs. Apo-SaFtsZ is essentially unfolded, as assessed by nuclear magnetic resonance and circular dichroism. Binding of GTP (>/= 1mM) dramatically shifts the equilibrium towards the active folded protein. Supportingly, SaFtsZ refolded with GDP crystallizes in a native structure. Apo-SaFtsZ also folds with 3.4 M glycerol, enabling high-affinity GTP binding (KD 20 nM determined by isothermal titration calorimetry) similar to thermophilic stable FtsZ. Other stabilizing agents that enhance nucleotide binding include ethylene glycol, trimethylamine N-oxide (TMAO), and several bacterial osmolytes. High salt stabilizes SaFtsZ without bound nucleotide in an inactive twisted conformation. We identified a cavity behind the SaFtsZ-GDP nucleotide-binding pocket that harbors different small compounds, which is available for extended nucleotide-replacing inhibitors. Furthermore, we devised a competition assay to detect any inhibitors that overlap the nucleotide site of SaFtsZ, or Escherichia coli FtsZ, employing osmolyte-stabilized apo-FtsZs and the specific fluorescence anisotropy change of mant-GTP upon dissociation from the protein. This robust assay provides a basis to screening for high affinity GTP-replacing ligands, which combined with structural studies and phenotypic profiling should facilitate development of a next generation of FtsZ-targeting antibacterial inhibitors. Nucleotide-induced folding of cell division protein FtsZ from Staphylococcus aureus.,Huecas S, Canosa-Valls AJ, Araujo-Bazan L, Ruiz FM, Laurents DV, Fernandez-Tornero C, Andreu JM FEBS J. 2020 Jan 29. doi: 10.1111/febs.15235. PMID:31997533 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cell division protein 3D structures

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