Secondary sphere interactions modulate peroxynitrite scavenging by the E2 domain of amyloid precursor protein.

ABSTRACT: Peroxynitrite (ONOO^-) is a highly reactive nitrogen species that can cause significant damage to proteins, lipids, and DNA. Various enzymes, including metalloenzymes, play crucial roles in reducing ONOO^- concentrations to protect cellular components. While the interaction of ONOO^- with heme proteins is well known, the reduction by Cu-containing proteins is less studied. Amyloid precursor protein (APP), implicated in Alzheimer's disease, has an E2 domain that binds copper ions with a dissociation constant of K_D ∼ 10^-12 M and is proposed to be involved in iron homeostasis, copper trafficking, and oxidative stress response. Our recent studies using EXAFS, UV-Vis, and EPR spectroscopy revealed a previously unidentified labile water

SUBMITTER: Zuercher EC 

PROVIDER: S-EPMC11640295 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature