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To prevent Cu binding to these sites, we generated several PrP mutants in which all of the octapeptide repeats were deleted (PrP-ΔOR), all histidine residues in the OR region were replaced with alanines (PrP-Ala1), or the histidine residues in both the OR and non-OR regions were substituted with alanine (PrP-Ala2) (Fig