We investigate the interaction of hemin with four fragments of prion protein (PrP) containing from one to four histidines (PrP106–114, PrP95–114, PrP84–114, PrP76–114) for its potential relevance to prion diseases and possibly traumatic brain injury. The binding properties of hemin-PrP complexes have been evaluated by UV–visible spectrophotometric titration. PrP peptides form a 1:1 adduct with hemin with affinity that increases with the number of histidines and length of the peptide; the following log K1 binding constants have been calculated: 6.48 for PrP76–114, 6.1 for PrP84– 114, 4.80 for PrP95–114, whereas for PrP106–114, the interaction is too weak to allow a reliable binding constant calculation. These constants are similar to that of amyloid-β (Aβ) for hemin, and similarly to hemin-Aβ, PrP peptides tend to form a six-coordinated low-spin complex. However, the concomitant aggregation of PrP induced by hemin prevents calculation of the K2 binding constant. The turbidimetry analysis of [hemin-PrP76–114] shows that, once aggregated, this complex is scarcely soluble and undergoes precipitation. Finally, a detailed study of the peroxidase-like activity of [hemin-(PrP)] shows a moderate increase of the reactivity with respect to free hemin, but considering the activity over long time, as for neurodegenerative pathologies, it might contribute to neuronal oxidative stress.
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