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Plumbagin inhibits cytokinesis in Bacillus subtilis by inhibiting FtsZ assembly - a mechanistic study of its antibacterial activity

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Title Plumbagin inhibits cytokinesis in Bacillus subtilis by inhibiting FtsZ assembly - a mechanistic study of its antibacterial activity
 
Creator BHATTACHARYA, A
JINDAL, B
SINGH, P
DATTA, A
PANDA, D
 
Subject antibacterial agent
bacterial cell division
FtsZ assembly
plumbagin
Z-ring
BACTERIAL-CELL DIVISION
ESCHERICHIA-COLI
ANTIMICROBIAL ACTIVITY
DRUG DISCOVERY
PROTEIN FTSZ
MYCOBACTERIUM-TUBERCULOSIS
INDUCED APOPTOSIS
GTPASE ACTIVITY
TARGETING FTSZ
CANCER CELLS
 
Description The assembly of FtsZ 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 Bacillussubtilis 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 FtsZ (BsFtsZ) with a dissociation constant of 20.7 +/- 5.6m, and inhibited the assembly and GTPase activity of BsFtsZ invitro. Interestingly, plumbagin did not inhibit either the assembly or GTPase activity of Escherichiacoli FtsZ (EcFtsZ) invitro. Using docking analysis, a putative plumbagin-binding site on BsFtsZ was identified, and the analysis indicated that hydrophobic interactions and hydrogen bonds predominate. Based on the insilico analysis, two variants of BsFtsZ, namely D199A and V307R, were constructed to explore the binding interaction of plumbagin and BsFtsZ. The effects of plumbagin on the assembly and GTPase activity of the variant BsFtsZ proteins invitro indicated that the residues D199 and V307 may be involved in the binding of plumbagin to BsFtsZ. The results suggest that plumbagin inhibits bacterial proliferation by inhibiting the assembly of FtsZ, and provide insight into the binding site of plumbagin on BsFtsZ, which may help in the design of potent FtsZ-targeted antibacterial agents.
 
Publisher WILEY-BLACKWELL
 
Date 2014-10-17T04:44:07Z
2014-10-17T04:44:07Z
2013
 
Type Article
 
Identifier FEBS JOURNAL, 280(18)4585-4599
1742-464X
1742-4658
http://dx.doi.org/10.1111/febs.12429
http://dspace.library.iitb.ac.in/jspui/handle/100/15980
 
Language en