title: Comparative analyses of the proteins from Mycobacterium tuberculosis and human genomes: Identification of potential tuberculosis drug targets.
abstract: Tuberculosis, one of the major infectious diseases affecting human beings is caused by the bacillus Mycobacterium tuberculosis. Increased resistance to known drugs commonly used for the treatment of tuberculosis has created an urgent need to identify new targets for validation and to develop drugs. In this study, we have used various bioinformatics tools, to compare the protein sequences from twenty-three M. tuberculosis genome strains along with the known human protein sequences, in order to identify the 'conserved' M. tuberculosis proteins absent in human. Further, based on the analysis of protein interaction networks, we selected one-hundred and forty proteins that were predicted as potential M. tuberculosis drug targets and prioritized according to the ranking of 'clusters' of interacting proteins. Comparison of the predicted 140 TB targets with literature indicated that 46 of them were previously reported, thereby increasing the confidence in our predictions of the remaining 94 targets too. The analyses of the structures and functions corresponding to the predicted potential TB drug targets indicated a diverse range of proteins that included ten 'druggable' targets with some of the known drugs.
authors.affiliation: Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India. Electronic address: sridhar@ccmb.res.in.
authors.forename: Settu
authors.initials: S
authors.lastname: Sridhar
authors.affiliation: Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India. Electronic address: pallabini@ccmb.res.in.
authors.forename: Pallabini
authors.initials: P
authors.lastname: Dash
authors.affiliation: Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India. Electronic address: guru@ccmb.res.in.
authors.forename: Kunchur
authors.initials: K
authors.lastname: Guruprasad
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D017124:Conserved Sequence; D015195:Drug Design; D015894:Genome, Human; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000378:metabolism; D060066:Protein Interaction Maps / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014376:Tuberculosis / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins
keywords: Amino acid sequence; Communicable diseases; Computational biology; Humans; Protein interaction maps; Tuberculosis