Dissertation/Thesis Abstract

Structure and Function of Iron-Sulfur Cluster Biosynthesis Proteins and the Influence of Oxygen Ligation
by Mansy, Sheref S., Ph.D., The Ohio State University, 2003, 272; 10834917
Abstract (Summary)

Members of the IscU family of proteins are among the most conserved of all protein groups, extending across all three kingdoms of life. IscU is believed to be involved in iron-sulfur cluster delivery to apo iron-sulfur proteins. However, most of the evidence supporting the function of IscU stems from genetic and cellular biological studies. Therefore, we set out to biochemically characterize human, yeast, and prokaryotic IscU proteins. A variety of spectroscopic techniques were used to evaluate IscU including, UV-visible absorption, Mössbauer, near- and far- UV circular dichroism, mass spectrometry, atomic absorption, and nuclear magnetic resonance. Herein we demonstrate that IscU proteins coordinate reductively labile [2Fe-2S]2+ centers and are capable of mediating delivery of intact cluster to apo protein targets. Furthermore, extensive structural and dynamic data of a hyperthermophilic homologue, Thermotoga maritima IscU, revealed that IscU adopts a mobile molten globule-like state that is vastly different from the previously identified ferredoxin-like fold that has thus far been characterized for other metallochaperones. Such a dynamic molecule may allow for the flexibility that is necessary for the multiple roles of Fe-S cluster assembly, and recognition and delivery of that cluster to a target protein. Additionally, we utilized X-ray crystallography to elucidate a high resolution structure of an oxygen ligated [4Fe-4S] high potential iron protein.

Indexing (document details)
Advisor: Cowan, James
Commitee:
School: The Ohio State University
Department: Biochemistry
School Location: United States -- Ohio
Source: DAI-B 79/09(E), Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Biochemistry
Keywords: High potential iron protein, Iron-sulfur cluster, Iscu, Metallochaperone, Nifu
Publication Number: 10834917
ISBN: 9780355946970
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