title: Glutathione-complexed [2Fe-2S] clusters function in Fe-S cluster storage and trafficking.
abstract: Glutathione-coordinated [2Fe-2S] complex is a non-protein-bound [2Fe-2S] cluster that is capable of reconstituting the human iron-sulfur cluster scaffold protein IscU. This complex demonstrates physiologically relevant solution chemistry and is a viable substrate for iron-sulfur cluster transport by Atm1p exporter protein. Herein, we report on some of the possible functional and physiological roles for this novel [2Fe-2S](GS4) complex in iron-sulfur cluster biosynthesis and quantitatively characterize its role in the broader network of Fe-S cluster transfer reactions. UV-vis and circular dichroism spectroscopy have been used in kinetic studies to determine second-order rate constants for [2Fe-2S] cluster transfer from [2Fe-2S](GS4) complex to acceptor proteins, such as human IscU, Schizosaccharomyces pombe Isa1, human and yeast glutaredoxins (human Grx2 and Saccharomyces cerevisiae Grx3), and human ferredoxins. Second-order rate constants for cluster extraction from these holo proteins were also determined by varying the concentration of glutathione, and a likely common mechanism for cluster uptake was determined by kinetic analysis. The results indicate that the [2Fe-2S](GS4) complex is stable under physiological conditions, and demonstrates reversible cluster exchange with a wide range of Fe-S cluster proteins, thereby supporting a possible physiological role for such centers.
authors: Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, Columbus, OH, 43210, USA.|The Biophysics Graduate Program, The Ohio State University, Columbus, USA.
authors: Insiya
authors: I
authors: Fidai
authors: Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, Columbus, OH, 43210, USA.|The Ohio State Biochemistry Program, The Ohio State University, Columbus, USA.
authors: Christine
authors: C
authors: Wachnowsky
authors: Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, Columbus, OH, 43210, USA. cowan@chemistry.ohio-state.edu.|The Biophysics Graduate Program, The Ohio State University, Columbus, USA. cowan@chemistry.ohio-state.edu.|The Ohio State Biochemistry Program, The Ohio State University, Columbus, USA. cowan@chemistry.ohio-state.edu.
authors: J A
authors: JA
authors: Cowan
mesh_terms: D001692:Biological Transport; D054477:Glutaredoxins / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D013455:Sulfur / Q000378:metabolism*
chemical_list: D054477:Glutaredoxins; C506160:ISCU protein, human; D007506:Iron-Sulfur Proteins; C547961:Isa1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D013455:Sulfur; D007501:Iron; D005978:Glutathione
keywords: Glutaredoxin; Glutathione; Iron-sulfur cluster; Isa; IscU