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The assembly of Fts Z plays a central role in construction of the cytokinetic Z-ring that orchestrates bacterial cell division. A naturally occurring naphthoquinone, plumbagin, is known to exhibit antibacterial properties against several types of bacteria. In this study, plumbagin was found to perturb formation of the Z-ring in Bacillus subtilis 168 cells and to cause elongation of these cells without an apparent effect on nucleoid segregation, indicating that it may inhibit FtsZ assembly. Furthermore, it bound to purified B. subtilis Fts Z ( Bs Fts Z) with a dissociation constant of 20.7 ± 5.6 μ m, and inhibited the assembly and GTPase activity of Bs Fts Z in vitro. Interestingly, plumbagin did not inhibit either the assembly or GTPase activity of Escherichia coli Fts Z ( Ec Fts Z) in vitro. Using docking analysis, a putative plumbagin-binding site on Bs Fts Z was identified, and the analysis indicated that hydrophobic interactions and hydrogen bonds predominate. Based on the in silico analysis, two variants of Bs Fts Z, namely D199 A and V307 R, were constructed to explore the binding interaction of plumbagin and Bs Fts Z. The effects of plumbagin on the assembly and GTPase activity of the variant Bs Fts Z proteins in vitro indicated that the residues D199 and V307 may be involved in the binding of plumbagin to Bs Fts Z. The results suggest that plumbagin inhibits bacterial proliferation by inhibiting the assembly of Fts Z, and provide insight into the binding site of plumbagin on Bs Fts Z, which may help in the design of potent Fts Z-targeted antibacterial agents. [ABSTRACT FROM AUTHOR]