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Structure elucidation study of aminoglycoside phosphotransferase from B. cereus sensu lato: a comprehensive outlook for drug discovery

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Abstract

Antibiotic resistance prevalent in various infectious pathogens towards diverse types of antimicrobials has emerged as a global cause of public health threat. The limitations in knowing the key drug binding sites of receptors in various resistance factors due to inadequacy of experimentally solved 3D structures have left resistance therapeutics research vague. Hence, in this study, we have demonstrated the importance of structure elucidation of aminoglycoside phosphotransferase (APH) enzyme from members of B. cereus sensu lato group by homology modeling technique. We have appropriately built 3D models of APH from volatile human pathogens like B. thuringiensis, B. mycoides, B. pseudomycoides, B. weihenstephanensis, and B. anthracis and validated them for stereochemical qualities. The Z-score analysis and structure superimposition study of template with homology models showed close resemblance of models with template 3TDW. The stereochemically validated model of APH from B. thuringiensis, B. mycoides, B. pseudomycoides, B. weihenstephanensis, and B. anthracis was deposited in the PMDB with identifier numbers as PM0082322, PM0082324, PM0082323, PM0082257, and PM0082321, respectively. The stability of all APH models was confirmed by performing molecular dynamics (MD) simulation for 50 ns. The undistorted behavior of secondary structure elements, i.e., helices and sheets from all APH models, was demonstrated using DSSP plot and found consistent over the entire simulation run. These APH models could be further explored for studying mechanism of resistance at molecular level and could be targeted for drug discovery. Thus, this study gives a comprehensive overview about the importance to structure elucidation for combating antibiotic resistance at the earliest.

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Data availability

Data in the form of 3D models of APH that support the findings of this study have been deposited in the PMDB (Protein Model DataBase) with PMDB IDs as PM0082322, PM0082324, PM0082323, PM0082257, and PM0082321.

Code availability

Not applicable.

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Acknowledgements

The authors are very much thankful to Computer Centre, Shivaji University, Kolhapur, for providing the computational facility.

Funding

This study was funded by UGC SAP Phase II (vide letter No. F. 4–8/2015/DRS-II (SAP-II) program sanctioned to Department of Biochemistry. KDS received financial support under UGC SAP Phase II (vide letter No. F. 4–8/2015/DRS-II (SAP-II) programme sanctioned to Department of Biochemistry, Shivaji University, Kolhapur, from University Grants Commission, New Delhi, UGC provided BSR fellowship under UGC SAP DRS Phase I programme (vide letter No.F.7–207/2009 (BSR) to RSP. DST SERB (EMR/2017/002688/BBM) and DST PURSE-II provided financial support to KDS. KDS also received from “DBT-BUILDER Shivaji University Interdisciplinary Life Science Programme for Advance Research and Education (No.: BT/INF/22/SP43063/2022; Date:11–03-2022)” sanctioned by Department of Biotechnology, Ministry of Science & Technology, Government of India.

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Authors and Affiliations

  1. Structural Bioinformatics Unit, Department of Biochemistry, Shivaji University, Kolhapur, 416004, Maharashtra, India

    Kailas D. Sonawane

  2. Department of Microbiology, Shivaji University, Kolhapur, 416004, Maharashtra, India

    Rishikesh S. Parulekar & Kailas D. Sonawane

  3. Department of Chemistry, Shivaji University, Kolhapur, 416004, Maharashtra, India

    Kailas D. Sonawane

Authors
  1. Rishikesh S. Parulekar
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  2. Kailas D. Sonawane
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Contributions

Dr.Kailas D. Sonawane contributed to the conceptualization and designing of the study. Dr. Rishikesh S. Parulekar performed material preparation, structural study, data analysis, and drafting of manuscript. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Kailas D. Sonawane.

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Highlights

• The 3D models of APH from members of B. cereus sensu lato group were built and deposited in PMDB.

• MD simulations for 50 ns confirmed the structural stability of all APH models.

• The DSSP plot revealed the conformational changes of APH models during MD simulation to explore the structural stability.

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Supplementary file1 (DOCX 1768 KB)

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Parulekar, R.S., Sonawane, K.D. Structure elucidation study of aminoglycoside phosphotransferase from B. cereus sensu lato: a comprehensive outlook for drug discovery. Struct Chem 34, 859–865 (2023). https://doi.org/10.1007/s11224-022-02040-9

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  • DOI: https://doi.org/10.1007/s11224-022-02040-9

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