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dc.contributor.advisor Franz, Katherine J en_US
dc.contributor.author Haas, Kathryn Louise en_US
dc.date.accessioned 2010-05-10T19:55:56Z
dc.date.available 2010-05-10T19:55:56Z
dc.date.issued 2010 en_US
dc.identifier.uri http://hdl.handle.net/10161/2373
dc.description Dissertation en_US
dc.description.abstract <p>Mechanisms of copper homeostasis are of great interest partly due to their connection to debilitating genetic and neurological disorders. The family of high-affinity copper transporters (Ctr) is responsible for extracellular copper acquisition and internalization in yeast, plants, and mammals, including human. The extracellular domain of the human high-affinity copper transporter (hCtr1) contains essential Cu-binding methionine-rich MXXM and MXM (Mets) motifs that are important for copper acquisition and transport. The hCtr1 extracellular domain also contains potential copper binding histidine (His) clusters, including a high-affinity Cu(II) ATCUN site. As of yet, extracellular His clusters have no established significance for hCtr1 function. We have made model peptides based on the extracellular copper acquisition domain of hCtr1 that is rich in His residues and Mets motifs. The peptides' Cu(I) and Cu(II) binding properties have been characterized by UV-Vis and mass spectrometry. Our findings have been extended to a mouse cell model and we show that His residues are important for hCtr1 function likely because of their contribution to strong copper-binding sites in the hCtr1 extracellular domain responsible for copper acquisition. </p> <p>Copper's pro-oxidant property is also medicinally promising if it can be harnessed to induce oxidative stress as a cancer chemotherapy strategy. Our lab has designed a photocleavable caged copper complex that can selectively release redox-active copper in response to light. The thermodynamic copper binding properties of these potential chemotherapeutics have been characterized</p> en_US
dc.format.extent 5201855 bytes
dc.format.mimetype application/pdf
dc.language.iso en_US
dc.subject Chemistry, Inorganic en_US
dc.subject Chemistry, Biochemistry en_US
dc.subject Caged Copper en_US
dc.subject Copper en_US
dc.subject Copper Transport en_US
dc.subject Ctr1 en_US
dc.subject Membrane Protein en_US
dc.subject Metal Homeostasis en_US
dc.title Copper at the Interface of Chemistry and Biology: New Insights into hCtr1 Function and the Role of Histidine in Human Cellular Copper Acquisition en_US
dc.type Dissertation en_US
dc.department Chemistry en_US
duke.embargo.months 6 en_US
dc.date.accessible 2010-05-18T05:00:39Z

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