It is estimated that a quarter of the world’s population is infected with Mycobacterium tuberculosis. Although New Zealand and Australia have some of the lowest incidence rates of tuberculosis, the disease disproportionally affects indigenous populations as well as migrant communities. With the emergence of multidrug-resistant TB, there is an urgent need to develop new treatments that target M. tuberculosis through novel mechanisms of action.
The Fe(II) and 2-oxoglutarate-dependent dioxygenase superfamily is one of the largest enzyme families. They are present in almost all living organisms and perform a range of important biological roles. This superfamily of enzymes is well characterised in many organisms including humans1, 2. However, they are relative unexplored in M. tuberculosis. Studies about the structure and function of these enzymes may therefore open new opportunities for future development of new treatments against tuberculosis. Herein, we report our work on the structural and mechanistic characterisation of RV3406, a putative alkyl sulfatase that has been implied in the antibiotic resistance mechanism against some antitubercular drugs3. By using mass spectrometry, nuclear magnetic resonance spectroscopy and protein X-ray crystallography, the structure and substrate specificity of this enzyme were explored. In addition, the inhibition of this enzyme was also studied, paving the way for the development of new antitubercular agents against this enzyme.