Sequence adaptation in various environments across organisms; similar yet different superoxide dismutase

Mycobacterium tuberculosis (M. tuberculosis) is a pathogenic bacterium that attack the host immune system and killed millions of people annually. The body first defense mechanism is through phagocytosis where an outburst of radical oxygen species (ROS) is released and potentially kill the bacterium. M. tuberculosis superoxide dismutase (MtSOD) survives the phagocytosis and suppresses the host immune system by converting reactive oxygen species to H2O2 and O2. SOD proteins are important for cell survival to prevent the buildup of reactive ROS in the cell that may cause damage to DNA, RNA, proteins, and even cell death. MtSOD (oxidized) is homologous to human SOD1 (hSOD1, reduced) which contains both zinc and copper metals along with the disulfide bond. Though, MtSOD lacks the zinc binding site which proposed to play a role in stability, dimerization, and function of SOD. Utilizing Circular Dichroism, an apparent correlation of MtSOD stabilization with the copper and disulfide bond as more stable secondary structure is observed for oxidized apoprotein compared to the reduced apo and oxidized holoprotein. To further investigate the novel role of zinc in SOD (ZnMtSOD), a mutation of zinc binding site consists of T119H, A123H, T192K (modeled from hSOD1) is introduced in the wild type MtSOD. With the low sequence identity of 19.7% but similar in protein structures, the thermodynamic and kinetics results are compared for hSOD1, ZnMtSOD, and wt MtSOD.