Prion diseases, such as Creutzfeldt-Jakob disease, Fatal Familial Insomnia, and Kuru, are fatal and incurable neurodegenerative diseases caused by misfolded prion proteins (PrP). While the mechanism behind infectious, misfolded PrP is better understood, the functional mechanism and purpose behind natively folded PrP is unknown. In this work, we use continuous wave (CW)-EPR to study the dynamics of a native Cu(II) binding site in PrP. The simultaneous interaction of this Cu(II) with the N- and C-terminal domain of PrP, i.e., the cis interaction, is proposed to enable regulation of the N-terminal domain by the C-terminal domain, preventing toxicity. Here, we perform mutations and deletions of residues in order to promote or inhibit the cis interaction. Because any observed dynamical changes reported by CW-EPR represent changes in the Cu(II) dynamics, we are able to determine how these mutations alter the involvement Cu(II) in the cis interaction.