6kvp

S. aureus FtsZ in complex with 3-(1-(5-bromo-4-(4-(trifluoromethyl)phenyl)oxazol-2-yl)ethoxy)-2,6-difluorobenzamide (compound 2)

spinqualitylabelsall models 6kvp, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6kvp 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 1.4Å Ligands: CA, GDP, ZI1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FTSZ_STAAR 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. Publication Abstract from PubMed Addressing the growing problem of antibiotic resistance requires the development of new drugs with novel antibacterial targets. FtsZ has been identified as an appealing new target for antibacterial agents. Here, we describe the structure-guided design of a new fluorescent probe (BOFP) in which a BODIPY fluorophore has been conjugated to an oxazole-benzamide FtsZ inhibitor. Crystallographic studies have enabled us to identify the optimal position for tethering the fluorophore that facilitates the high-affinity FtsZ binding of BOFP. Fluorescence anisotropy studies demonstrate that BOFP binds the FtsZ proteins from the Gram-positive pathogens Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus pneumoniae with Kd values of 0.6-4.6 microM. Significantly, BOFP binds the FtsZ proteins from the Gram-negative pathogens Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii with an even higher affinity (Kd = 0.2-0.8 microM). Fluorescence microscopy studies reveal that BOFP can effectively label FtsZ in all the above Gram-positive and Gram-negative pathogens. In addition, BOFP is effective at monitoring the impact of non-fluorescent inhibitors on FtsZ localization in these target pathogens. Viewed as a whole, our results highlight the utility of BOFP as a powerful tool for identifying new broad-spectrum FtsZ inhibitors and understanding their mechanisms of action. Structure-Guided Design of a Fluorescent Probe for the Visualization of FtsZ in Clinically Important Gram-Positive and Gram-Negative Bacterial Pathogens.,Ferrer-Gonzalez E, Fujita J, Yoshizawa T, Nelson JM, Pilch AJ, Hillman E, Ozawa M, Kuroda N, Al-Tameemi HM, Boyd JM, LaVoie EJ, Matsumura H, Pilch DS Sci Rep. 2019 Dec 27;9(1):20092. doi: 10.1038/s41598-019-56557-x. PMID:31882782 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cell division protein 3D structures

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