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Insights On Iron-Sulfur Cluster Assembly Donor Proteins

Dizin, Eric Michel

Abstract Details

2008, Doctor of Philosophy, Ohio State University, Chemistry.

Iron-sulfur clusters are an important class of prosthetic group involved in electron transfer, enzyme catalysis, and regulation of gene expression. Their biosynthesis requires a complex machinery located within the mitochondrion since free iron and sulfide are extremely toxic to the cell. This research has focused on the three central proteins dedicated to the assembly: a cysteine desulfurase, Nfs1, an iron donor protein, frataxin, and an iron-sulfur cluster scaffold protein, Isu1.

Human Nfs1, a PLP dependent enzyme, catalyzes the decomposition of cysteine to alanine and forms a persulfide bond with a conserved cysteine residue. To date, Nfs1 has only been partially characterized. Furthermore, its hyperproduction relies on yeast organisnm, Pichia pastoris, which is cumbersome and leads to quite low yields. Therefore, we undertook to design a bacterial expression system by cloning and overexpressing the gene in different E. coli strain. This enabled only a partial characterization of the cysteine desulfurase.

Besides being an iron donor for iron-sulfur cluster assembly, frataxin has also been implicated in heme biosynthesis, and in iron storage in the mitochondrion with reported ferroxidase activity. We decided to further investigate its ability to bind to other metals, such as magnesium, calcium, and zinc, and also studied its ferroxidase activity as a mature and as a truncated protein. We concluded that frataxin has negligible ferroxidase activity, comparable to iron, and quite distinct from ferritin. Moreover frataxin binds zinc besides iron, but with a different stoichiometry.

James Cowan, PhD (Advisor)
Claudia Turro, PhD (Committee Member)
Thomas Magliery, PhD (Committee Member)
113 p.

Recommended Citations

Citations

  • Dizin, E. M. (2008). Insights On Iron-Sulfur Cluster Assembly Donor Proteins [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1208532379

    APA Style (7th edition)

  • Dizin, Eric. Insights On Iron-Sulfur Cluster Assembly Donor Proteins. 2008. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1208532379.

    MLA Style (8th edition)

  • Dizin, Eric. "Insights On Iron-Sulfur Cluster Assembly Donor Proteins." Doctoral dissertation, Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1208532379

    Chicago Manual of Style (17th edition)