Fig. 4. Visual inspection of 3D structures of PAPs shows how orientation of Tyr and Trp alters flap elevation. In case of PlmII, altered Trp and Tyr orientation (PDB:2BJU,162IGY17 and 4Z22 (ref. 18)) leads to expansion of the binding site (grey: 1LF4, blue: 2BJU, green: 2IGY, magenta: 4Z22). In case of cathepsin-D, high pH alters the conformation of Tyr which leads to flap elevation (blue: 1LYW,19 grey: 1LYA20). Alternative conformation of Tyr was also observed in case of BACE-1 (blue: 1SGZ, grey: 3TPL).
