Kaur, Gundeep and Kapoor, Srajan and Kaundal, Soni and Dutta, Dipak and Thakur, Krishan Gopal (2020) Structure-Guided Designing and Evaluation of Peptides Targeting Bacterial Transcription. Frontiers in bioengineering and biotechnology, 8. ISSN 2296-4185

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Abstract

The mycobacterial RNA polymerase (RNAP) is an essential and validated drug target for developing antibacterial drugs. The β-subunit of Mycobacterium tuberculosis (Mtb) RNAP (RpoB) interacts with an essential and global transcription factor, CarD, and confers antibiotic and oxidative stress resistance to Mtb. Compromising the RpoB/CarD interactions results in the killing of mycobacteria, hence disrupting the RpoB/CarD interaction has been proposed as a novel strategy for the development of anti-tubercular drugs. Here, we describe the first approach to rationally design and test the efficacy of the peptide-based inhibitors which specifically target the conserved PPI interface between the bacterial RNAP β/transcription factor complex. We performed in silico protein-peptide docking studies along with biochemical assays to characterize the novel peptide-based inhibitors. Our results suggest that the top ranked peptides are highly stable, soluble in aqueous buffer, and capable of inhibiting transcription with IC50 > 50 μM concentration. Using peptide-based molecules, our study provides the first piece of evidence to target the conserved RNAP β/transcription factor interface for designing new inhibitors. Our results may hence form the basis to further improve the potential of these novel peptides in modulating bacterial gene expression, thus inhibiting bacterial growth and combating bacterial infections.

Item Type:	Article
Additional Information:	The copyright of this article belongs to Frontiers Media.
Uncontrolled Keywords:	RNA polymerase; CarD; peptide-based inhibitors; Mycobacterium tuberculosis; bacterial transcription; protein-protein interaction
Subjects:	Q Science > QR Microbiology
Depositing User:	Dr. K.P.S.Sengar
Date Deposited:	29 Oct 2020 06:51
Last Modified:	29 Oct 2020 06:51
URI:	http://crdd.osdd.net/open/id/eprint/2615

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