Unraveling the potential of intrinsically disordered proteins as drug targets: application to Mycobacterium tuberculosis.
Many eukaryotic and prokaryotic proteins remain disordered under physiological conditions and often acquire a stable secondary structure on binding to their cellular targets. Though the process of binding is still under analysis, it has been found that the flexibility of proteins can add to their functionality. This motivated us to explore intrinsically disordered proteins (IDPs) as drug targets. In silico studies have been carried out on Mycobacterium tuberculosis, which, with emergence of hyper-virulent and drug resistant strains, XDRs and MDRs, is one of the most dreaded pathogens in the modern world. Our study reports 13 IDPs as potential drug targets, and three of them--FtsW (Rv2154c), GlmU (Rv1018c) and Obg (Rv2440c)--are chosen as key proteins and are described in detail. Future applications of this method can provide new insight into understanding the molecular mechanism of IDPs and their potential role as drug targets.
Anurag
Meenakshi
M
G.N.R. Knowledge Center of Genome Informatics, Institute of Genomics and Integrative Biology, CSIR, New Delhi, 110007, India.
Dash
Debasis
D
D000995:Antitubercular Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D016503:Drug Delivery Systems / Q000379:methods*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000378:metabolism; D025941:Protein Interaction Mapping; D020543:Proteome / Q000235:genetics / Q000378:metabolism
D000995:Antitubercular Agents; D001426:Bacterial Proteins; C532100:GlmU protein, Mycobacterium tuberculosis; D008565:Membrane Proteins; D009097:Multienzyme Complexes; C090542:Obg GTP-binding protein, Bacteria; D020543:Proteome; C061684:FtsW protein, Bacteria; D019204:GTP-Binding Proteins