{"id":{"repo_id":"lsu-thes","oai_identifier":"oai:repository.lsu.edu:gradschool_dissertations-1669"},"canonical_url":"https://search.dev.ndltd.org/etd/lsu-thes/oai:repository.lsu.edu:gradschool_dissertations-1669","repository":{"repo_id":"lsu-thes","name":"Lousiana State University","base_url":"https://repository.lsu.edu/do/oai/"},"display":{"title":"Biogenesis of iron-sulfur clusters and intracellular iron metabolism","abstract":"Iron-sulfur ([Fe-S]) clusters represent one of natures most diverse and ubiquitous protein prosthetic groups. [Fe-S] proteins are integral for diverse biological processes. Reconstitution of apo-proteins can occur by exogenously adding excess iron and sulfide. However, due to the toxicity of iron and sulfide, it is most likely that proteins coordinate [Fe-S] cluster assembly in cells. The first part of this dissertation addressed the iron donor for [Fe-S] cluster assembly. Recently, it has been shown that IscA is capable of binding iron with an association constant of 3.0 x 10<sup>19</sup>M<sup>-1</sup>. In addition, iron-loaded IscA is capable of donating iron to the proposed scaffold IscU for nascent [Fe-S] cluster assembly. We show that hIscA, the human homolog of <i>E. coli</i> IscA, functions as an iron chaperone for the assembly of [Fe-S] clusters in <i>E. coli</i> IscU. hIscA’s iron binding ability is similar to <i>E. coli</i> IscA. Moreover, hIscA is able to donate iron to IscU in the presence of 100-fold excess citrate, a metabolite capable of binding iron. This comparison signifies that [Fe-S] cluster assembly is conserved from bacteria to humans. The second part of this dissertation determined the participation of Ferritin A (FtnA) in [Fe-S] cluster assembly. FtnA, the major iron storage protein in <i>E. coli</i>, could serve as an iron reservoir when intracellular iron is depleted. We have shown that FtnA is capable of buffering iron when oxidative stress disrupts nascent [Fe-S] clusters and alleviates the production of hydroxyl radicals. Moreover, when physiological conditions return, IscA is able to retrieve iron from FtnA for [Fe-S] cluster assembly. The final part of this dissertation corroborated the interrelatedness of the oxidative and nitrosative stress response pathways. NsrR, a nitric oxide (NO) sensitive transcriptional repressor, is shown to coordinate a redox active [2Fe-2S] cluster with a midpoint redox potential of -346 ± 7 mV. The NsrR [2Fe-2S] cluster reacts with NO more quickly than other [Fe-S] proteins, signifying its role as a NO sensor. Finally, modification of the NsrR [2Fe-2S] cluster by NO results in the formation of a protein-bound dinitrosyl iron complex, relieving its DNA binding ability as a repressor.","abstract_html":"Iron-sulfur ([Fe-S]) clusters represent one of natures most diverse and ubiquitous protein prosthetic groups. [Fe-S] proteins are integral for diverse biological processes. Reconstitution of apo-proteins can occur by exogenously adding excess iron and sulfide. However, due to the toxicity of iron and sulfide, it is most likely that proteins coordinate [Fe-S] cluster assembly in cells. The first part of this dissertation addressed the iron donor for [Fe-S] cluster assembly. Recently, it has been shown that IscA is capable of binding iron with an association constant of 3.0 x 10&lt;sup&gt;19&lt;/sup&gt;M&lt;sup&gt;-1&lt;/sup&gt;. In addition, iron-loaded IscA is capable of donating iron to the proposed scaffold IscU for nascent [Fe-S] cluster assembly. We show that hIscA, the human homolog of &lt;i&gt;E. coli&lt;/i&gt; IscA, functions as an iron chaperone for the assembly of [Fe-S] clusters in &lt;i&gt;E. coli&lt;/i&gt; IscU. hIscA’s iron binding ability is similar to &lt;i&gt;E. coli&lt;/i&gt; IscA. Moreover, hIscA is able to donate iron to IscU in the presence of 100-fold excess citrate, a metabolite capable of binding iron. This comparison signifies that [Fe-S] cluster assembly is conserved from bacteria to humans. The second part of this dissertation determined the participation of Ferritin A (FtnA) in [Fe-S] cluster assembly. FtnA, the major iron storage protein in &lt;i&gt;E. coli&lt;/i&gt;, could serve as an iron reservoir when intracellular iron is depleted. We have shown that FtnA is capable of buffering iron when oxidative stress disrupts nascent [Fe-S] clusters and alleviates the production of hydroxyl radicals. Moreover, when physiological conditions return, IscA is able to retrieve iron from FtnA for [Fe-S] cluster assembly. The final part of this dissertation corroborated the interrelatedness of the oxidative and nitrosative stress response pathways. NsrR, a nitric oxide (NO) sensitive transcriptional repressor, is shown to coordinate a redox active [2Fe-2S] cluster with a midpoint redox potential of -346 ± 7 mV. The NsrR [2Fe-2S] cluster reacts with NO more quickly than other [Fe-S] proteins, signifying its role as a NO sensor. Finally, modification of the NsrR [2Fe-2S] cluster by NO results in the formation of a protein-bound dinitrosyl iron complex, relieving its DNA binding ability as a repressor.","abstract_has_math":false,"creators":["Bitoun, Jacob Philip"],"institution":"Biological Sciences","degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2009,"date_issued":"2009-01-01T08:00:00Z","date_published":"2009-01-01T08:00:00Z","updated_at":"2026-07-24T02:57:56Z","subjects":["operon","Bacterioferritin","DNIC","EPR","transcription","reduction","oxidation"],"languages":[],"rights":["unrestricted","Release the entire work immediately for access worldwide."],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["etd-07092009-144958","https://repository.lsu.edu/gradschool_dissertations/670"],"render_values":[{"text":"etd-07092009-144958","href":null,"code":true},{"text":"https://repository.lsu.edu/gradschool_dissertations/670","href":"https://repository.lsu.edu/gradschool_dissertations/670","code":true}]}]},"links":{"outbound_url":"https://doi.org/10.31390/gradschool_dissertations.670","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Bitoun, Jacob Philip"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2009-06-26"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2022-05-12T23:09:36Z"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Biological Sciences"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["operon","Bacterioferritin","DNIC","EPR","transcription","reduction","oxidation"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["unrestricted","Release the entire work immediately for access worldwide."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["etd-07092009-144958","10.31390/gradschool_dissertations.670","https://repository.lsu.edu/gradschool_dissertations/670"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Iron-sulfur ([Fe-S]) clusters represent one of natures most diverse and ubiquitous protein prosthetic groups. [Fe-S] proteins are integral for diverse biological processes. Reconstitution of apo-proteins can occur by exogenously adding excess iron and sulfide. However, due to the toxicity of iron and sulfide, it is most likely that proteins coordinate [Fe-S] cluster assembly in cells. The first part of this dissertation addressed the iron donor for [Fe-S] cluster assembly. Recently, it has been shown that IscA is capable of binding iron with an association constant of 3.0 x 10<sup>19</sup>M<sup>-1</sup>. In addition, iron-loaded IscA is capable of donating iron to the proposed scaffold IscU for nascent [Fe-S] cluster assembly. We show that hIscA, the human homolog of <i>E. coli</i> IscA, functions as an iron chaperone for the assembly of [Fe-S] clusters in <i>E. coli</i> IscU. hIscA’s iron binding ability is similar to <i>E. coli</i> IscA. Moreover, hIscA is able to donate iron to IscU in the presence of 100-fold excess citrate, a metabolite capable of binding iron. This comparison signifies that [Fe-S] cluster assembly is conserved from bacteria to humans. The second part of this dissertation determined the participation of Ferritin A (FtnA) in [Fe-S] cluster assembly. FtnA, the major iron storage protein in <i>E. coli</i>, could serve as an iron reservoir when intracellular iron is depleted. We have shown that FtnA is capable of buffering iron when oxidative stress disrupts nascent [Fe-S] clusters and alleviates the production of hydroxyl radicals. Moreover, when physiological conditions return, IscA is able to retrieve iron from FtnA for [Fe-S] cluster assembly. The final part of this dissertation corroborated the interrelatedness of the oxidative and nitrosative stress response pathways. NsrR, a nitric oxide (NO) sensitive transcriptional repressor, is shown to coordinate a redox active [2Fe-2S] cluster with a midpoint redox potential of -346 ± 7 mV. The NsrR [2Fe-2S] cluster reacts with NO more quickly than other [Fe-S] proteins, signifying its role as a NO sensor. Finally, modification of the NsrR [2Fe-2S] cluster by NO results in the formation of a protein-bound dinitrosyl iron complex, relieving its DNA binding ability as a repressor."]},{"key":"dc:title","label":"Title","values":["Biogenesis of iron-sulfur clusters and intracellular iron metabolism"]}]}],"canonical_facts":{"dc:creator":["Bitoun, Jacob Philip"],"dc:date":["2009-06-26"],"dc:date.available":["2022-05-12T23:09:36Z"],"dc:description.abstract":["Iron-sulfur ([Fe-S]) clusters represent one of natures most diverse and ubiquitous protein prosthetic groups. [Fe-S] proteins are integral for diverse biological processes. Reconstitution of apo-proteins can occur by exogenously adding excess iron and sulfide. However, due to the toxicity of iron and sulfide, it is most likely that proteins coordinate [Fe-S] cluster assembly in cells. The first part of this dissertation addressed the iron donor for [Fe-S] cluster assembly. Recently, it has been shown that IscA is capable of binding iron with an association constant of 3.0 x 10<sup>19</sup>M<sup>-1</sup>. In addition, iron-loaded IscA is capable of donating iron to the proposed scaffold IscU for nascent [Fe-S] cluster assembly. We show that hIscA, the human homolog of <i>E. coli</i> IscA, functions as an iron chaperone for the assembly of [Fe-S] clusters in <i>E. coli</i> IscU. hIscA’s iron binding ability is similar to <i>E. coli</i> IscA. Moreover, hIscA is able to donate iron to IscU in the presence of 100-fold excess citrate, a metabolite capable of binding iron. This comparison signifies that [Fe-S] cluster assembly is conserved from bacteria to humans. The second part of this dissertation determined the participation of Ferritin A (FtnA) in [Fe-S] cluster assembly. FtnA, the major iron storage protein in <i>E. coli</i>, could serve as an iron reservoir when intracellular iron is depleted. We have shown that FtnA is capable of buffering iron when oxidative stress disrupts nascent [Fe-S] clusters and alleviates the production of hydroxyl radicals. Moreover, when physiological conditions return, IscA is able to retrieve iron from FtnA for [Fe-S] cluster assembly. The final part of this dissertation corroborated the interrelatedness of the oxidative and nitrosative stress response pathways. NsrR, a nitric oxide (NO) sensitive transcriptional repressor, is shown to coordinate a redox active [2Fe-2S] cluster with a midpoint redox potential of -346 ± 7 mV. The NsrR [2Fe-2S] cluster reacts with NO more quickly than other [Fe-S] proteins, signifying its role as a NO sensor. Finally, modification of the NsrR [2Fe-2S] cluster by NO results in the formation of a protein-bound dinitrosyl iron complex, relieving its DNA binding ability as a repressor."],"dc:identifier":["etd-07092009-144958","10.31390/gradschool_dissertations.670","https://repository.lsu.edu/gradschool_dissertations/670"],"dc:rights":["unrestricted","Release the entire work immediately for access worldwide."],"dc:subject":["operon","Bacterioferritin","DNIC","EPR","transcription","reduction","oxidation"],"dc:title":["Biogenesis of iron-sulfur clusters and intracellular iron metabolism"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"],"thesis:institution_name":["Biological Sciences"]},"updated_at":"2026-07-24T02:57:56Z"}