Abstract
Background
Among the resistant isolates of MTB, multidrug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) have been the areas of growing concern. The genomic analysis showed that the respective genomic pool of the XDR-MTB proteome contains more than 30% of the hypothetical proteins for which no functions have been annotated yet. This class of proteins presumably have their own importance to complete genome and proteome information. The bioinformatics advancements have helped to annotate those hypothetical proteins by using various computational tools and have potential to classify them functionally.
Objective
The objective of this study was to propose a new and unique drug target against the deadly Mycobacterium tuberculosis using Bioinformatics approaches to characterize the hypothetical proteins.
Results
We stepwise reduced the hypothetical proteins (total number: 1256) out of the complete proteome to only 26 essential hypothetical proteins. Out of those 26 proteins, the protein WP_003401246.1 was computationally characterized as the druggable target.
Conclusion
The study proposed a hypothetical protein from complete proteome of the XDR-MTB as a new drug target against which new drug candidates can be proposed. Hence, the study opens up the new avenues in the areas of drug discovery against deadly M. tuberculosis.
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Acknowledgements
The authors would like to gratefully acknowledge the Higher Education Commission of Pakistan for providing the financial support (Grant # 20-3420/NRPU/R&D/HEC/14/1093) for this study.
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Reaz Uddin, Quratulain Nehal Siddiqui, Muhammad Sufian, Syed Sikander Azam and Abdul Wadood declare that they have no conflict of interest.
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13258_2019_857_MOESM1_ESM.pdf
All the computational commands and scripts used in this study are provided as github repository here: https://github.com/mriazuddin/HypotheticalProteins Supplementary File S1: The multiple sequence alignment from CLC Sequence viewer (PDF 1957 kb)
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Uddin, R., Siddiqui, Q.N., Sufian, M. et al. Proteome-wide subtractive approach to prioritize a hypothetical protein of XDR-Mycobacterium tuberculosis as potential drug target. Genes Genom 41, 1281–1292 (2019). https://doi.org/10.1007/s13258-019-00857-z
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DOI: https://doi.org/10.1007/s13258-019-00857-z