Copper is an essential element for all living organisms. However, due to its low redox potential it can be involved in the production of reactive oxygen species; where excess amounts of copper can be exceptionally toxic.1 In humans, malfunctions in copper metabolism are linked to diseases such as Menkes syndrome, Wilson’s disease, prion disease, and Alzheimer’s disease.2 Maintenance of copper homeostasis requires a number of proteins, such as copper transporters and chaperones to deliver copper to the correct protein while limiting free copper in the cell.3 Therefore, understanding the thermodynamics of copper(II) coordination in proteins is critical to our understanding of copper homeostasis. Herein we report human carbonic anhydrase II contains a novel copper binding site with picomolar affinity.4 A full characterization of the structure and thermodynamics associated with the coordination of both Cu atoms into their respective sites is discussed. Techniques including paramagnetic nuclear magnetic resonance spectroscopy (NMR), and x-ray absorption spectroscopy (XAS) techniques provide insight into the high affinity CuA coordination environment. A detailed characterization of this high affinity binding site and related peptide-bound model complexes are included, with the results providing insights into the chemistry and physiological impact of copper binding in human carbonic anhydrase II.
| Identifer | oai:union.ndltd.org:MSSTATE/oai:scholarsjunction.msstate.edu:td-2190 |
| Date | 09 December 2016 |
| Creators | Nettles, Whitnee Leigh |
| Publisher | Scholars Junction |
| Source Sets | Mississippi State University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
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