Homology modelling of a sensor histidine kinase from Aeromonas hydrophila |
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Authors: | Mobashar Hussain Urf Turabe Fazil Sunil Kumar Naidu Subbarao Haushila Prasad Pandey Durg Vijai Singh |
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Institution: | (1) Infectious Disease Biology, Institute of Life Sciences, Nalco Square, Bhubaneswar, 751023, India;(2) Bioinformatics Centre, Institute of Life Sciences, Nalco Square, Bhubaneswar, 751023, India;(3) Centre for Computational Biology and Bio-informatics, School of Information Technology, Jawaharlal Nehru University, New Delhi, 110067, India;(4) Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi, 221005, India; |
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Abstract: | Aeromonas hydrophila has been implicated in extra-intestinal infection and diarrhoea in humans. Targetting unique effectors of bacterial pathogens
is considered a powerful strategy for drug design against bacterial variations to drug resistance. The two-component bacterial
system involving sensor histidine kinase (SHK) and its response regulators is considered a lucrative target for drug design.
This is the first report describing a three-dimensional (3D) structure for SHK of A. hydrophila. The model was constructed by homology modelling using the X-ray structure of PleD—a response regulator—in conjunction with
cdiGMP (PDB code 1W25) and HemAT sensor domain (PDB code 1OR4)—a globin coupled sensor. A combination of homology modelling
methodology and molecular dynamics (MD) simulations was applied to obtain a reasonable structure to understand the dynamic
behaviour of SHK. Homology modelling was performed using MODELLER9v2 software. The structure was relaxed to eliminate bad
atomic contacts. The final model obtained by molecular mechanics and dynamics methods was assessed using PROCHECK and VERIFY
3D graph, which confirmed that the final refined model is reliable. Until complete biochemical and structural data of SHK
are determined by experimental means, this model can serve as a valuable reference for characterising the protein and could
be explored for drug targetting by design of suitable inhibitors. |
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