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Homology modelling of a sensor histidine kinase from Aeromonas hydrophila

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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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Abbreviations

SHK:

Sensor histidine kinase

EM:

Energy minimisation

BLAST:

Basic local alignment search tool

MDS:

Molecular dynamics simulation

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Acknowledgements

The study was supported by funds contributed by the Department of Biotechnology to the Institute of Life Sciences, Bhubaneswar, India. A Senior Research Fellowship to M.H.U.T.F. awarded by Indian Council of Medical Research, New Delhi is kindly acknowledged. S.K. was supported by Distributed Information Sub-centre of Institute of Life Sciences, Bhubaneswar. We thank Dr. Sanjeev Kumar Singh and Mr. Sunil Tripathi for their help with the molecular dynamics simulation study.

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Authors and Affiliations

  1. Infectious Disease Biology, Institute of Life Sciences, Nalco Square, Bhubaneswar, 751023, India

    Mobashar Hussain Urf Turabe Fazil & Durg Vijai Singh

  2. Bioinformatics Centre, Institute of Life Sciences, Nalco Square, Bhubaneswar, 751023, India

    Sunil Kumar

  3. Centre for Computational Biology and Bio-informatics, School of Information Technology, Jawaharlal Nehru University, New Delhi, 110067, India

    Naidu Subbarao

  4. Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi, 221005, India

    Haushila Prasad Pandey

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  1. Mobashar Hussain Urf Turabe Fazil
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  2. Sunil Kumar
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  3. Naidu Subbarao
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  4. Haushila Prasad Pandey
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  5. Durg Vijai Singh
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Correspondence to Durg Vijai Singh.

Additional information

Mobashar Hussain Urf Turabe Fazil and Sunil Kumar contributed equally to this work.

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Fazil, M.H.U.T., Kumar, S., Subbarao, N. et al. Homology modelling of a sensor histidine kinase from Aeromonas hydrophila . J Mol Model 16, 1003–1009 (2010). https://doi.org/10.1007/s00894-009-0602-2

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