Chauhan, Neeraj Kumar and Anand, Anjali and Sharma, Arun and Dhiman, Kanika and Gosain, Tannu Priya and Singh, Prashant and Singh, Padam and Khan, Eshan and Chattopadhyay, Gopinath and Kumar, Amit and Sharma, Deepak and Sharma, Tarun Kumar and Singh, Ramandeep Structural and Functional Characterization of Rv0792c from Mycobacterium tuberculosis: Identifying Small Molecule Inhibitor against HutC Protein. MICROBIOLOGY SPECTRUM.
Full text not available from this repository. (Request a copy)Abstract
In order to adapt in host tissues, microbial pathogens regulate their gene expression through a variety of transcription factors. Here, we have functionally characterized Rv0792c, a HutC homolog from Mycobacterium tuberculosis. In comparison to the parental strain, a strain of M. tuberculosis with a Rv0792c mutant was compromised for survival upon exposure to oxidative stress and infection in guinea pigs. RNA sequencing analysis revealed that Rv0792c regulates the expression of genes involved in stress adaptation and virulence of M. tuberculosis. Solution small-angle X-ray scattering (SAXS) data-steered model building confirmed that the C-terminal region plays a pivotal role in dimer formation. Systematic evolution of ligands by exponential enrichment (SELEX) resulted in the identification of single-strand DNA (ssDNA) aptamers that can be used as a tool to identify small-molecule inhibitors targeting Rv0792c. Using SELEX and SAXS data-based modeling, we identified residues essential for Rv0792c’s aptamer binding activity. In this study, we also identified I-OMe-Tyrphostin as an inhibitor of Rv0792c’s aptamer and DNA binding activity. The identified small molecule reduced the growth of intracellular M. tuberculosis in macrophages. The present study thus provides a detailed shape-function characterization of a HutC family of transcription factor from M. tuberculosis.
| Item Type: | Article |
|---|---|
| Additional Information: | The copyright of this article belongs to ASM |
| Uncontrolled Keywords: | Mycobacterium tuberculosis, GntR transcription factors, HutC subfamily, bacterial pathogenesis, aptamer, SELEX, SAXS, small molecule inhibitor |
| Subjects: | Q Science > QR Microbiology |
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 07 Jun 2023 05:27 |
| Last Modified: | 07 Jun 2023 05:27 |
| URI: | http://crdd.osdd.net/open/id/eprint/3069 |
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