Reaz Uddin1, Quratulain Nehal Siddiqui2, Muhammad Sufian2, Syed Sikander Azam3, Abdul Wadood4. 1. Lab 103 PCMD ext. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan. mriazuddin@iccs.edu. 2. Lab 103 PCMD ext. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan. 3. National Centre for Bioinformatics, Quaid-i-Azam University, Islamabad, Pakistan. 4. Department of Biochemistry, Abdul Wali Khan University, Mardan, Pakistan.
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.
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.
Entities:
Keywords:
Drug resistance; Drug targets; Hypothetical proteins; Molecular docking; Mycobacterium tuberculosis; Protein structure; Proteome; Subtractive genomics
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