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Journal of Biosciences

, Volume 40, Issue 1, pp 13–30 | Cite as

Structural studies on Mycobacterium tuberculosis RecA: Molecular plasticity and interspecies variability

  • Anu V Chandran
  • J Rajan Prabu
  • Astha Nautiyal
  • K Neelakanteshwar Patil
  • K Muniyappa
  • M VijayanEmail author
Article

Abstract

Structures of crystals of Mycobacterium tuberculosis RecA, grown and analysed under different conditions, provide insights into hitherto underappreciated details of molecular structure and plasticity. In particular, they yield information on the invariant and variable features of the geometry of the P-loop, whose binding to ATP is central for all the biochemical activities of RecA. The strengths of interaction of the ligands with the P-loop reveal significant differences. This in turn affects the magnitude of the motion of the ‘switch’ residue, Gln195 in M. tuberculosis RecA, which triggers the transmission of ATP-mediated allosteric information to the DNA binding region. M. tuberculosis RecA is substantially rigid compared with its counterparts from M. smegmatis and E. coli, which exhibit concerted internal molecular mobility. The interspecies variability in the plasticity of the two mycobacterial proteins is particularly surprising as they have similar sequence and 3D structure. Details of the interactions of ligands with the protein, characterized in the structures reported here, could be useful for design of inhibitors against M. tuberculosis RecA.

Keywords

Homologous recombination molecular flexibility Mycobacterial RecA P-loop species variation 

Notes

Acknowledgements

Intensity data were collected at the Facility for Protein X-ray Structure Determination and Protein Design, supported by the Department of Science and Technology (DST), European Synchrotron Radiation Facility at Grenoble (access arranged by DBT) and Elettra synchrotron Light Source, Trieste (access arranged by DST). Part of the computations was carried out at the Interactive Graphics Facility, supported by the DBT. KM is the recipient of J.C. Bose National Fellowship from the DST. MV is the Albert Einstein Research Professor of the Indian National Science Academy. The work was supported by a research grant from DBT.

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Copyright information

© Indian Academy of Sciences 2014

Authors and Affiliations

  • Anu V Chandran
    • 1
  • J Rajan Prabu
    • 1
  • Astha Nautiyal
    • 2
  • K Neelakanteshwar Patil
    • 2
  • K Muniyappa
    • 2
  • M Vijayan
    • 1
    Email author
  1. 1.Molecular Biophysics UnitIndian Institute of ScienceBangaloreIndia
  2. 2.Department of BiochemistryIndian Institute of ScienceBangaloreIndia

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