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Molecular dynamics simulation of the Staphylococcus aureus YsxC protein: molecular insights into ribosome assembly and allosteric inhibition of the protein

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Abstract

YsxC from Staphylococcus aureus is a member of the GTPase protein family, and is involved in the ribosomal assembly and stability of this microorganism through its interactions with the L17, S2 and S10 ribosomal proteins. Inhibition of its interactions with L17, S2, S10 and the β′ subunit of RNA polymerase influences ribosomal assembly, which may affect the growth of the microorganism. This makes YsxC a novel target for the design of inhibitors to treat the disease caused by S. aureus. Understanding the interaction mechanism between YsxC and its partners would aid in the identification of potential catalytic residues, which could then be targeted to inhibit its function. Accordingly, in the present study, an in silico analysis of the interactions between YsxC and L17, S2 and S10 was performed, and the potential residues involved in these interactions were identified. Based on the simulation results, a possible mechanism for the interactions between these proteins was also proposed. Finally, six ligands from among a library of 81,000 chemical molecules were found to interact with parts of the G2 and switch II regions of the YsxC protein. Moreover, their interactions with the YsxC protein were observed to provoke changes at its GTP-binding site, which suggests that the binding of these ligands leads to a reduction in GTPase activity, and they were also found to affect the interactions of YsxC with its partners. This observation indicates that the proposed interacting site of YsxC may act as an allosteric site, and disrupting interactions at this site might lead to novel allosteric inhibition of the YsxC protein.

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Acknowledgments

RK, Manivel and Kannan thank the University Grants Commission, Government of India (UGC) for funding this Major Research Project, and the Rajiv Gandhi National Fellowship for also providing funding assistance. Research at the Laboratory of the Centre for Excellence in Bioinformatics, Pondicherry University, India is funded by the Department of Information Technology (DIT) and the Department of Biotechnology (DBT), Government of India, New Delhi, India.

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  1. Centre of Excellence in Bioinformatics, School of Life Sciences, Pondicherry University, Puducherry, 605 014, India

    Amit Goyal, Kannan Muthu, Manivel Panneerselvam, Anil Kumar Pole & Krishna Ramadas

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  1. Amit Goyal
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  2. Kannan Muthu
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  3. Manivel Panneerselvam
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Correspondence to Krishna Ramadas.

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Amit Goyal and Muthu Kannan contributed equally to this work.

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Goyal, A., Muthu, K., Panneerselvam, M. et al. Molecular dynamics simulation of the Staphylococcus aureus YsxC protein: molecular insights into ribosome assembly and allosteric inhibition of the protein. J Mol Model 17, 3129–3149 (2011). https://doi.org/10.1007/s00894-011-0998-3

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