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

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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.

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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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Authors and Affiliations

  1. Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560 012, India

    Anu V Chandran, J Rajan Prabu & M Vijayan

  2. Department of Biochemistry, Indian Institute of Science, Bangalore, 560 012, India

    Astha Nautiyal, K Neelakanteshwar Patil & K Muniyappa

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  1. Anu V Chandran
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  2. J Rajan Prabu
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  4. K Neelakanteshwar Patil
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  5. K Muniyappa
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Correspondence to M Vijayan.

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Corresponding editor: B Jagadeeshwar Rao

[Chandran AV, Prabu JR, Nautiyal A, Patil KN, Muniyappa K and Vijayan M 2015 Structural studies on Mycobacterium tuberculosis RecA: Molecular plasticity and interspecies variability. J. Biosci. 40 1–18] DOI 10.1007/s12038-014-9497-x

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Chandran, A.V., Prabu, J.R., Nautiyal, A. et al. Structural studies on Mycobacterium tuberculosis RecA: Molecular plasticity and interspecies variability. J Biosci 40, 13–30 (2015). https://doi.org/10.1007/s12038-014-9497-x

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