Raja, S and Paul, A and Raghavan, S and Narayanan, S and Shee, S and Singh, A and Varshney, U and Gopal, B and Vijayan, M (2022) Structural variability of Mycobacterium tuberculosis SSB and susceptibility to inhibition. In: Current Science, 122 (3). pp. 281-289.
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Abstract
Single-stranded DNA is formed at various stages of DNA metabolism. It is protected from degradation by single-stranded DNA-binding proteins (SSBs). Struc-tural variability has been observed in the quaternary arrangement of tetrameric SSBs from mycobacteria and other sources. Here we describe two novel crystal forms which illustrate the extent of structural varia-bility. Docking studies carried out with inhibitors identified from DNA-binding assays allowed the char-acterization of eight distinct potential binding regions or grooves on each tetramer that circumvent structurally variable regions. Compounds known to inhibit certain bacterial SSBs were tested against Mycobacterium tu-berculosis SSB (MtSSB) using DNA-binding and cellu-lar assays. We report two compounds that inhibit MtSSB and growth of the bacterium. Together, this structural analysis reveals a strategy to exploit the variability of MtSSB for the design of inhibitors to this protein. The variability in structure of MtSSB could contribute to its susceptibility to inhibition.
| Item Type: | Journal Article |
|---|---|
| Publication: | Current Science |
| Publisher: | Indian Academy of Sciences |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Keywords: | Binding regions; Crystal structure; Docking; Inhibitor development; Mycobacterium tuberculosis; Structural plasticity |
| Department/Centre: | Division of Biological Sciences > Molecular Biophysics Unit Division of Biological Sciences > Microbiology & Cell Biology Division of Biological Sciences > Centre for Infectious Disease Research |
| Date Deposited: | 24 Jun 2022 12:04 |
| Last Modified: | 24 Jun 2022 12:04 |
| URI: | https://eprints.iisc.ac.in/id/eprint/73866 |
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