Proteome-wide subtractive approach to prioritize a hypothetical protein of XDR-Mycobacterium tuberculosis as potential drug target

被引:23
作者
Uddin, Reaz [1 ]
Siddiqui, Quratulain Nehal [1 ]
Sufian, Muhammad [1 ]
Azam, Syed Sikander [2 ]
Wadood, Abdul [3 ]
机构
[1] Univ Karachi, Int Ctr Chem & Biol Sci, Lab PCMD Ext Dr Panjwani Ctr Mol Med & Drug Res 1, Karachi 75270, Pakistan
[2] Quaid i Azam Univ, Natl Ctr Bioinformat, Islamabad, Pakistan
[3] Abdul Wali Khan Univ, Dept Biochem, Mardan, Pakistan
关键词
Proteome; Subtractive genomics; Drug resistance; Mycobacterium tuberculosis; Drug targets; Hypothetical proteins; Molecular docking; Protein structure; STRUCTURE PREDICTION; GLYCOSYLTRANSFERASES; IDENTIFICATION; CLASSIFICATION; DATABASE;
D O I
10.1007/s13258-019-00857-z
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1281 / 1292
页数:12
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