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

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.