Abstract

Resistance to many of the current antibacterial agents are now an alarming health problem worldwide, necessitating a proactive effort to find attractive target for new antibacterial drug discovery. Filamenting temperature-sensitive mutant Z (FtsZ), an analogue of eukaryotic tubulin, is an essential and highly conserved bacterial cytokinesis protein considered as attractive target for anti-bacterial drug discovery. Curcumin, a naturally occurring dietary polyphenolic compound is found to bind to FtsZ in vitro with a dissociation constant of 7.3±1.8 μM. It induced filamentation in the Bacillus subtilis 168, suggesting that it inhibited the assembly of FtsZ protofilaments and also increased the GTPase activity of FtsZ. Conformational analysis and geometry optimization of curcumin was performed according to the Hartree- Fock (HF) calculation method by ArgusLab 4.0.1 software. The protein binding energy calculation and docking simulations were carried out by in silico studies using the tool AutoDock 4.0. The three dimensional (3D) structures of the Bacillus subtilis FtsZ with bound potassium ion (PDB code: 2VXY) with a resolution factor of 1.7 Å was retrieved from the RCSB Protein Data Bank. The observed docking result predicts high binding affinity of the curcumin and analogue 12 suggest that these compounds are potentially more potent than PC190723, a known inhibitor of FtsZ.

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