Effect of Mutation and Disulfide Bond Formation on the Catalytic Site of Monomeric Cytoglobin: A Molecular Level Insight

Cytoglobin (Cygb) is one of recently discovered member of the globin family. Cygb maintains a large apolar cavity with the heme group located in it. The main catalytic activity of Cygb takes place around this heme group, which is also considered as a ligand docking station. It was explored by biochemical experiments that Cygb can scavenge reactive oxygen and nitrogen species, such as hydrogen peroxide, nitric oxide and peroxinitrite, protecting the cell against oxidative and nitrosative stress. However, the effect of mutation as well as its synergistic effect together with oxidation on scavenging activity of the Cygb has not been studied yet in details. Thus, in this research we perform molecular dynamics and docking simulations to study the impact of mutation and oxidation on the Cygb catalytic function. Our simulation results show that the mutation of lysine 80 residue to alanine in Cygb results in an opening of the access to the heme group, thereby increasing its scavenging function. Moreover, the combination of this mutation (i.e., Cygb(L80A)) with the oxidation (namely, the disulfide bond formation in Cygb (i.e., CygbS-S)) induces the complex conformational changes in its structure. As a result, these changes lead to even more opening of the access to the heme group, which in turn enhances the scavenging activity of Cygb to a more extend. The latter can be a hallmark of enhanced enzymatic function of the modified Cygb (i.e., Cygb(L80A) and CygbS-S).

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