Glutathione Complexed Fe–S Centers

Abstract

Glutathione (γ-glutamyl-cysteinyl-glycine, GSH) is a major thiol-containing peptide with cellular levels of up to 10 mM. Several recent reports have demonstrated glutaredoxins (Grx) to form [Fe₂S₂] cluster-bridged dimers, where glutathione provides two exogenous thiol ligands, and have implicated such species in cellular iron sulfur cluster biosynthesis. We report the finding that glutathione alone can coordinate and stabilize an [Fe₂S₂] cluster under physiological conditions, with optical, redox, Mössbauer, and NMR characteristics that are consistent with a [Fe₂S₂]­(GS)₄ composition. The Fe–S assembly protein ISU catalyzes formation of [Fe₂S₂]­(GS)₄ from iron and sulfide ions in the presence of glutathione, and the [Fe₂S₂] core undergoes reversible exchange between apo ISU and free glutathione