Single Point Mutation from E22-to-K in Aβ Initiates Early-Onset Alzheimer’s Disease by Binding with Catalase

Figure 2

The effects of E22K and Aβ binding with catalase on H₂O₂ levels. (a) The schedule of intrahippocampal injection with saline (Con), Aβ, Aβ plus L-cys, E22K, and E22K plus L-cys and a chemical reaction between L-cys and H₂O₂ (above). DG: dentate gyrus. The identification of the local injection trace in the brains of SD rats by immunochemistry (below). (b) Brain catalase activity and H₂O₂ concentrations in rats analyzed by commercial kits (, ). (c) Brain catalase activity and H₂O₂ concentrations in rats analyzed by commercial kits (, ). ; ^##. Data are the . (d) The simulated three-dimensional (3D) crystal structures of Aβ binding with catalase simulated by Discovery studio 3.0. Catalase (CAT, PDB ID: 1DGF); Aβ (PDB ID: 1IYT). (e) The binding motif, four molecules of HEME (blue), in catalase. (f) Histine 74 (H74, yellow) and asparagine 147 (N147, purple) are the binding sites of H₂O₂. Tyrosine 357 (Y357, cyan) is the active center of catalase for Fe(III) oxidation to Fe(IV). (g) The distance between alanine 30 (A30, red) of Aβ and Y357 (cyan) of catalase (over 6 Å). (h–k) The simulated 3D structure of E22K binding with catalase (green), HEME group (blue): four porphyrin heme (iron) groups, H74 (yellow), N47 (purple), and Y357 (cyan). (k) The distance between alanine 30 (A30, red) of E22K and Y357 (cyan) of catalase (less 6 Å).

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