Glutathione-complexed iron-sulfur clusters. Reaction intermediates and evidence for a template effect promoting assembly and stability.

Assembly and stabilization of a glutathione-complexed [2Fe-2S] cluster is promoted by aggregation of glutathione. The cluster core selects the tetramer species from a collection of equilibrating solution aggregate species, and in turn the core is stabilized toward hydrolytic degradation. Studies of glutathione derivatives, in combination with mass spectrometric and Mössbauer investigations provide insight on reaction intermediates during formation of [2Fe-2S](GS)4(2-).

Glutathione complexed Fe-S centers.

Glutathione (γ-glutamyl-cysteinyl-glycine, GSH) is a major thiol-containing peptide with cellular levels of up to 10 mM. (1) Several recent reports have demonstrated glutaredoxins (Grx) to form [Fe(2)S(2)] 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 [Fe(2)S(2)] cluster under physiological conditions, with optical, redox, Mössbauer, and NMR characteristics that are consistent with a [Fe(2)S(2)](GS)(4) composition.