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Targeting Aminoglycoside Acetyltransferase Activity of Mycobacterium tuberculosis (H37Rv) Derived Eis (Enhanced Intracellular Survival) Protein with Quercetin

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Abstract

Eis (Enhanced intracellular survival) protein is an aminoglycoside acetyltransferase enzyme classified under the family – GNAT (GCN5-related family of N-acetyltransferases) secreted by Mycobacterium tuberculosis (Mtb). The enzymatic activity of Eis results in the acetylation of kanamycin, thereby impairing the drug’s action. In this study, we expressed and purified recombinant Eis (rEis) to determine the enzymatic activity of Eis and its potential inhibitor. Glide-enhanced precision docking was used to perform molecular docking with chosen ligands. Quercetin was found to interact Eis with a maximum binding affinity of -8.379 kcal/mol as compared to other ligands. Quercetin shows a specific interaction between the positively charged amino acid arginine in Eis and the aromatic ring of quercetin through π-cation interaction. Further, the effect of rEis was studied on the antibiotic activity of kanamycin A in the presence and absence of quercetin. It was observed that the activity of rEis aminoglycoside acetyltransferase decreased with increasing quercetin concentration. The results from the disk diffusion assay confirmed that increasing the concentration of quercetin inhibits the rEis protein activity. In conclusion, quercetin may act as a potential Eis inhibitor.

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Acknowledgements

As part of the ICMR-SRF program, Logesh Radhakrishnan acknowledges the ICMR, New Delhi, for providing an SRF fellowship (File No. 2020-0056/CMB-BMS dated 12/02/2021). For permitting the utilization of Far UV-CD equipment, the authors are grateful to Dr. Athi N. Naganathan of the IIT, Madaras. The authors thank the BSA Crescent Institute of Science and Technology for providing lab space and facilities.

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Authors and Affiliations

  1. School of Life Sciences, B. S. Abdur Rahman Crescent Institute of Science & Technology, Vandalur, Chennai, Tamil Nadu, 600048, India

    Logesh Radhakrishnan, Shazia Jamal & Neesar Ahmed

  2. Department of Biotechnology, Bhupat & Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, Tamil Nadu, 600036, India

    Rahul Dani

  3. School of Pharmacy, BSA Crescent Institute of Science and Technology, Vandalur, Chennai, Tamil Nadu, 600048, India

    Irfan Navabshan

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  1. Logesh Radhakrishnan
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  5. Neesar Ahmed
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Contributions

NA and SJ conceived and designed the methodology and research. LR and RD conducted the experiments and NA and IN analyzed the data. LR, SJ and NA wrote the manuscript analyzed the final results. All the authors read and approved the manuscript.

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Correspondence to Neesar Ahmed.

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Radhakrishnan, L., Dani, R., Navabshan, I. et al. Targeting Aminoglycoside Acetyltransferase Activity of Mycobacterium tuberculosis (H37Rv) Derived Eis (Enhanced Intracellular Survival) Protein with Quercetin. Protein J 43, 12–23 (2024). https://doi.org/10.1007/s10930-023-10165-x

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