cAMP Receptor Protein (CRP) / Fumarate Nitrate Reductase Regulator (FNR) family proteins are ubiquitous regulators of cell stress in eubacteria. These proteins are commonly associated with maintenance of intracellular oxygen levels, redox-state, oxidative and nitrosative stresses, and extreme temperature conditions by regulating expression of target genes that contain regulatory cognate DNA elements. We describe the use of informatics enabled comparative genomics to identify novel genes under the control of CRP regulator including the operon context of potentially regulated genes. We present regulons in four mycobacterial species, namely Mycobacterium tuberculosis (Mtb), M. leprae, M. avium paratuberculosis and M. smegmatis. We also report biochemical and biophysical characterization of recombinant MtbCRP and the characterization of the recombinant protein in terms of DNA binding and ligand binding. Further we have carried out crystallization and X-ray diffraction studies on this protein. In final part of this work, we have solved X-ray crystal structure of MtbCRP in complex with DNA and cAMP (pdb entry: 3MZH).