TY  - JOUR
N1  - The copyright of this article belongs to ASM 
ID  - open3075
UR  - https://journals.asm.org/doi/10.1128/spectrum.01973-22
IS  - 1
A1  - Chauhan, Neeraj Kumar
A1  - Anand, Anjali
A1  - Sharma, Arun
A1  - Dhiman, Kanika
A1  - Gosain, Tannu Priya
A1  - Singh, Prashant
A1  - Singh, Padam
A1  - Khan, Eshan
A1  - Chattopadhyay, Gopinath
A1  - Kumar, Amit
A1  - Sharma, Deepak
A1  - Sharma, Tarun Kumar
A1  - Singh, Ramandeep
Y1  - 2022/12/11/
N2  - 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.
PB  - ASM
JF  - MICROBIOLOGY SPECTRUM
VL  - 11
KW  - Mycobacterium tuberculosis
KW  -  GntR transcription factors
KW  -  HutC subfamily
KW  -  bacterial pathogenesis
KW  -  aptamer
KW  -  SELEX
KW  -  SAXS
KW  -  small molecule inhibitor
TI  - Structural and Functional Characterization of Rv0792c from Mycobacterium tuberculosis: Identifying Small Molecule Inhibitor against HutC Protein
ER  -