Figure 8.
Four APPI mutations optimize intra- and intermolecular packing interactions with KLK6. A and B, side view of the primed side of the substrate-binding cleft between KLK6 residues 39–41 (salmon surfaces) and Phe-151 (lavender) portrays van der Waals packing interactions in complexes with APPIWT (cyan) (A) and APPI-4M (mutated residues shown in yellow) (B). The mutated residues Leu-17, Phe-19, and Val-34 of APPI-4M form a hydrophobic cluster that fills the crevice and form hydrophobic interactions with KLK6 residues Phe-151 and Leu-40, whereas Phe-19 also forms a ring-stacking interaction with KLK6 His-39. C and D, rotated view, revealing how the mutated residues Phe-18 and Phe-19 of APPI-4M wrap around the ridge formed by KLK6 residues 39–41 (D), thus forming a more extensive contact interface than in the APPIWT/KLK6 complex (C).