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(A–D) Comparison of the locations of APP substrate residues P1′, P2′, and P3′ in the (A) wildtype active, (B) I45F active, (C) T48P active, and (D) shifted active M51F APP substrate-bound conformations of γ-secretase. (E) Comparison of the corresponding PS1 active-site S1′, S2′, and S3′ pockets in these different conformational states of γ-secretase.
