FIGURE 1.

Structures of clitocypin (A and B), macrocypin (C), and schematic representation of trefoil fold (D). The trunk strands are always shown in red, and the crown strands are in yellow. A, the view from the side is shown. The structure resembles a tree structure, with two loops in the root region, a stem built of a six-stranded β-barrel, and two layers of loops (6 + 3) in the crown region. The first layer of the crown loops is shown in green, and the second is in blue. B and C, shown is the view along the barrel. The binding loops for cathepsins are marked with blue arrows, and the AEP loop is marked with green arrows. The two loops that bind to cysteine cathepsins belong to the lower layer of crown loops, whereas a single loop from the root region can inhibit trypsin or AEP.