Dioxygen activation in the Cu-amyloid β complex.

Area of Science:

• Biochemistry
• Neuroscience
• Computational Chemistry

Background:

• Amyloid beta (Aβ) peptides and copper (Cu) are implicated in neurodegenerative diseases.
• Oxidative stress, involving ascorbate and dioxygen, contributes to neuronal death in the synapse.
• The interaction between Cu, Aβ, and dioxygen is a critical early step in this oxidative process.

Purpose of the Study:

• To investigate the binding mechanism of dioxygen to Cu(I)-amyloid beta complexes.
• To elucidate the role of this binding in the activation of copper ligands and surrounding residues.
• To understand the atomic-level details of dioxygen activation in the context of neurodegeneration.

Main Methods:

• Density-functional theory (DFT) calculations were employed.
• The study focused on the atomic interactions between Cu(I)-Aβ and dioxygen.
• Analysis of the coordination environment and electronic structure was performed.

Main Results:

• Dioxygen binding to Cu(I) within the Aβ complex is feasible.
• Dioxygen activation occurs under specific conditions, favoring a square-planar Cu(2+) coordination.
• Aspartate 1 carboxylate plays a role in dioxygen activation by coordinating to copper anti to O2.

Conclusions:

• The binding of dioxygen to Cu(I)-Aβ is a critical step initiating oxidative stress in neurodegeneration.
• Specific coordination environments, involving negatively charged residues, are essential for dioxygen activation.
• This research provides atomic-level insights into the molecular mechanisms underlying neurodegenerative processes.