Mutagenic Activation of Glutathione Peroxidase-4: Approaches toward Rational Design of Allosteric Drugs.

ABSTRACT: Glutathione peroxidase 4 (GPX4) reduces lipid hydroperoxides in lipid membranes, effectively inhibiting iron-dependent cell death or ferroptosis. The upregulation of the enzyme by the mutations at residues D21 and D23 has been suggested to be associated with higher protein activity, which confers more protection against neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases. Therefore, it has become an attractive target for treating and preventing neurodegenerative diseases. However, identifying means of mimicking the beneficial effects of these mutations distant from the active site constitutes a formidable challenge in moving toward therapeutics. In this study, we explore using molecular dynamics simulations to computationally map the conformational and en

SUBMITTER: Ma C 

PROVIDER: S-EPMC9434792 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature