Structure Based Discovery of inhibitors for Multidrug Efflux Pump- AcrB
Rahul Ramtekkar1, Waheeta Hopper2, M. Michael Gromiha3, Kazuhiko Fukui4D. Velmurugan1,5*
Affiliation
- 1Center of Advanced Study in Crystallography and Biophysics, University of Madras, Maraimalai (Guindy) Campus, Chennai, India
- 2Department of Bioinformatics, School of Bioengineering, Faculty of Engineering and Technology, SRM University, Kattankulathur
- 3Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India
- 4Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan
- 5Bioinformatics Infrastructure Facility, University of Madras, Maraimalai (Guindy) Campus, Chennai, India
Corresponding Author
Velmurugan, D. Center of Advanced Study in Crystallography and Biophysics, University of Madras, Maraimalai (Guindy) Campus, Chennai – 600 025, India; E-mail: shirai2011@gmail.com
Citation
Velmurugan, D., et al. Structure Based Discovery of inhibitors for Multidrug Efflux Pump-AcrB (2015) Bioinfo Proteom Img Anal 1(2): 27 -35.
Copy rights
© 2015 Velmurugan, D. This is an Open access article distributed under the terms of Creative Commons Attribution 4.0 International License.
Abstract
In Escherischia coli, AcrB is an inner membrane transporter that cooperates with a membrane fusionprotein, AcrA and an outer membrane channel TolC, to export a wide variety of drugs directly out of the cell, bypassing the periplasm. By overproducing such membrane transport proteins, E. coli and other human pathogenic bacteria are able to achieve multidrug resistance. In this paper, we have reported the virtual screening of five in silico small molecule libraries against the substrate recognition site situated in the porter domain of binding protomer of AcrB using tools of Schrödinger suite, which resulted in six potential hits. All these compounds favored hydrogen bonding interactions with mainly polar and aromatic residues such as Ser134, Phe178 and Ile671. From the observed results these ligands are suggested to be potent candidates for inhibiting AcrB. Docking simulations were also carried out with several known substrates and inhibitors in order to study their interactions with the binding site.
