Figure EV5. Helical peptide inhibitors target a substrate‐binding site different from the exosites.

1. Helical peptide GSIs D‐10 and D‐13 mimicking TMD segments V36‐I45 (D‐10) and V36‐T48 (D‐13) of APP and targeting a putative exosite termed docking site (D‐10) or both docking site and active site (D‐13) (Kornilova et al, 2005) do not compete for substrate binding at exosites, suggesting that docking site and exosites are distinct. 10, D‐10; 13, D‐13.
2. Inhibition of substrate binding in the active site by D‐10 and D‐13 suggests that these GSIs interfere with substrate binding before or at the active site.