6KVQ

S. aureus FtsZ in complex with BOFP (compound 3)

6KVQ の概要

• エントリーDOI: 10.2210/pdb6kvq/pdb
• 分子名称: Cell division protein FtsZ, GUANOSINE-5'-DIPHOSPHATE, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: gtpase, protein-inhibitor complex, hydrolase
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33117.58

構造登録者

Ferrer-Gonzalez, E.,Fujita, J.,Yoshizawa, T.,Nelson, J.M.,Pilch, A.J.,Hillman, E.,Ozawa, M.,Kuroda, N.,Parhi, A.K.,LaVoie, E.J.,Matsumura, H.,Pilch, D.S. (登録日: 2019-09-05, 公開日: 2020-01-15, 最終更新日: 2023-11-22)

主引用文献

Ferrer-Gonzalez, E.,Fujita, J.,Yoshizawa, T.,Nelson, J.M.,Pilch, A.J.,Hillman, E.,Ozawa, M.,Kuroda, N.,Al-Tameemi, H.M.,Boyd, J.M.,LaVoie, E.J.,Matsumura, H.,Pilch, D.S.
Structure-Guided Design of a Fluorescent Probe for the Visualization of FtsZ in Clinically Important Gram-Positive and Gram-Negative Bacterial Pathogens.
Sci Rep, 9:20092-20092, 2019

PubMed Abstract: 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 K values of 0.6-4.6 µM. 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 (K = 0.2-0.8 µM). 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.

PubMed: 31882782
DOI: 10.1038/s41598-019-56557-x

実験手法

X-RAY DIFFRACTION (1.6 Å)