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Access Type

WSU Access

Date of Award

January 2022

Degree Type


Degree Name



Biochemistry and Molecular Biology

First Advisor

Bharati Mitra


Transition metals are important for maintaining life as they catalyze important enzymatic reactions, provide structural support for proteins, and regulate cellular functions. Despite their importance, transition metals are toxic in excess concentrations. Therefore, their levels need to be regulated. Transport proteins are a critical component of transition metal regulation. The P1-Type ATPase and ZIP family of proteins constitute two important families of transport proteins, which function to regulate transition level metals in both bacteria and humans. ZntA and ZupT are the two functioning proteins from Escherichia coli that represent these two families. Their study can illuminate conserved properties with human homologs. This work focuses on understanding the molecular properties of these two proteins with an emphasis on the metal binding sites in each. It was found that a novel splice variant from ATP7B modeled with ZntA had an altered meta binding stoichiometry, driven by a confirmational change in dimerization. For ZupT, it was found that zinc and iron had distinct metal binding sites and had cooperative transport. The role of manganese transport by ZupT was also examined. Together this work presents lacking biochemical characterization to compliment the extensive cell and animal model knowledge.

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