Biophysical and Catalytic Characterization of Gpx7 in Presence Divalent Metal Ions

Abstract

Glutathione peroxidase (GPx) is a family of proteins found in biological systems. The protein family is known to detoxicate the system by scavenging reactive oxygen species, formed upon interaction of the system with external moieties or stress conditions or normally synthesized during metabolism of the system. Out of all members of the family, GPx4 and 7 stand alone because of their action on lipid peroxides. GPx4 and 7 are known to reduce lipid peroxides present in lipid membrane into respective lipid alcohol, hence saving the membrane from depolarization. Besides GPx7, other proteins (GPx1-6) of the family are very much known to scientific community. Hence, the underlying mechanism of detoxification by GPx7 is under the scientific scanner. To this end, the thesis has employed extensive in silico studies to draw a picture of GPx-7 relations with other proteins of the family, and the possible catalysis efficiency of the protein in presence of different metal ions. In addition, in vitro studies (partially) started to validate the catalysis findings from in silico studies. The in silico findings indicate that cysteine has been re-favored over selenocysteine residue during the evolutionary development of proteins in the family. In addition, the protein share relatively higher propensity for the non-polar environment than other proteins of the family. On catalysis efficiency of the protein, GPx-7 has highest affinity for lipid peroxide in presence of Ca2+ ions, and least in presence of Se2+ . However, the protein loses its affinity for lipid peroxide in presence of Mg2+ or Fe2+ ions.