GPX4

2GS3, 2OBI2879625249ENSG00000167468ENSMUSG00000075706P36969Q91XR9O70325NM_002085NM_001039847NM_001039848NM_001367832NM_001037741NM_008162NM_001367995NP_001034936NP_001034937NP_002076NP_001354761NP_001032830.2NP_001032830NP_032188NP_001354924Glutathione peroxidase 4, also known as GPX4, is an enzyme that in humans is encoded by the GPX4 gene. GPX4 is a phospholipid hydroperoxidase that protects cells against membrane lipid peroxidation.2gs3: Crystal structure of the selenocysteine to glycine mutant of human glutathione peroxidase 4(GPX4) Glutathione peroxidase 4, also known as GPX4, is an enzyme that in humans is encoded by the GPX4 gene. GPX4 is a phospholipid hydroperoxidase that protects cells against membrane lipid peroxidation. The antioxidant enzyme glutathione peroxidase 4 (GPx4) belongs to the family of glutathione peroxidases, which consists of 8 known mammalian isoenzymes (GPx1-8). Gpx4 catalyzes the reduction of hydrogen peroxide, organic hydroperoxides, and lipid peroxides at the expense of reduced glutathione and functions in the protection of cells against oxidative stress. The oxidized form of glutathione (glutathione disulfide), which is generated during the reduction of hydroperoxides by GPx4, is recycled by glutathione reductase and NADPH/H+. GPx4 differs from the other GPx family members in terms of its monomeric structure, a less restricted dependence on glutathione as reducing substrate, and the ability to reduce lipid-hydroperoxides inside biological membranes. Inactivation of GPX4 leads to an accumulation of lipid peroxides, resulting in ferroptotic cell death. Mutations in GPX4 cause spondylometaphyseal dysplasia. Mammalian GPx1, GPx2, GPx3, and GPx4 (this protein) have been shown to be selenium-containing enzymes, whereas GPx6 is a selenoprotein in humans with cysteine-containing homologues in rodents. In selenoproteins, the 21st amino acid selenocysteine is inserted in the nascent polypeptide chain during the process of translational recoding of the UGA stop codon. GPx4 shares the amino acid motif of selenocysteine, glutamine, and tryptophane (catalytic triad) with other glutathione peroxidases.