Fig. 4: Comparison between the “Active” and “I5” low-energy conformational states in γ-secretase. | Communications Biology

Fig. 4: Comparison between the “Active” and “I5” low-energy conformational states in γ-secretase.

From: Effects of presenilin-1 familial Alzheimer’s disease mutations on γ-secretase activation for cleavage of amyloid precursor protein

Fig. 4: Comparison between the “Active” and “I5” low-energy conformational states in γ-secretase.

a The “Active” low-energy conformational state of WT PS1, where the distance between residues D257 and D385 is ~7.0 Å. A water molecule formed hydrogen bonds with the two catalytic aspartates and poised for the ε cleavage of the amide bond between residues L49–V50 of APP. b The “I5” low-energy conformational state of L166P FAD mutant PS1, where the distance between the two catalytic aspartates D257 and D385 is too large at ~8.5 Å to trap a water molecule for the ε cleavage of APP. c Location of APP substrate residues P1’, P2’, and P3’ in the “I5” low-energy conformational state compared to “Active” WT. The “Active” and “I5” low-energy conformational states are shown in green and blue, respectively.

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