Please use this identifier to cite or link to this item: https://doi.org/10.1021/bi7018546
Title: Berberine targets assembly of Escherichia coli cell division protein FtsZ
Authors: Domadia, P.N.
Bhunia, A.
Sivaraman, J. 
Swarup, S. 
Dasgupta, D.
Issue Date: 11-Mar-2008
Citation: Domadia, P.N., Bhunia, A., Sivaraman, J., Swarup, S., Dasgupta, D. (2008-03-11). Berberine targets assembly of Escherichia coli cell division protein FtsZ. Biochemistry 47 (10) : 3225-3234. ScholarBank@NUS Repository. https://doi.org/10.1021/bi7018546
Abstract: The ever increasing problem of antibiotic resistance necessitates a search for new drug molecules that would target novel proteins in the prokaryotic system. FtsZ is one such target protein involved in the bacterial cell division machinery. In this study, we have shown that berberine, a natural plant alkaloid, targets Escherichia coli FtsZ, inhibits the assembly kinetics of the Z-ring, and perturbs cytokinesis. It also destabilizes FtsZ protofilaments and inhibits the FtsZ GTPase activity. Saturation transfer difference NMR spectroscopy of the FtsZ-berberine complex revealed that the dimethoxy groups, isoquinoline nucleus, and benzodioxolo ring of berberine are intimately involved in the interaction with FtsZ. Berberine perturbs the Z-ring morphology by disturbing its typical midcell localization and reduces the frequency of Z-rings per unit cell length to half. Berberine binds FtsZ with high affinity (K D ∼ 0.023 μM) and displaces bis-ANS, suggesting that it may bind FtsZ in a hydrophobic pocket. Isothermal titration calorimetry suggests that the FtsZ-berberine interaction occurs spontaneously and is enthalpy/entropy-driven. In silico molecular modeling suggests that the rearrangement of the side chains of the hydrophobic residues in the GTP binding pocket may facilitate the binding of the berberine to FtsZ and lead to inhibition of the association between FtsZ monomers. Together, these results clearly indicate the inhibitory role of berberine on the assembly function of FtsZ, establishing it as a novel FtsZ inhibitor that halts the first stage in bacterial cell division. © 2008 American Chemical Society.
Source Title: Biochemistry
URI: http://scholarbank.nus.edu.sg/handle/10635/100160
ISSN: 00062960
DOI: 10.1021/bi7018546
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

109
checked on Jul 16, 2018

WEB OF SCIENCETM
Citations

102
checked on Jun 26, 2018

Page view(s)

40
checked on May 18, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.