Fig. 3.

The interaction of PKS21004 with the human i-20S. a Detailed hydrophobic interactions between the R1 and R3 groups of PKS21004 with the substrate pocket of the human β5i subunit. A hydrogen bond between Ser27 and the oxygen atom of the PKS21004 R3 group (3.0 Å) is shown as a dashed red line. b Interactions of the R2 and R3 groups of PKS21004 with the neighboring β6 subunit. The strong H-bond between Asp125 and the nitrogen atom of the R2 of PKS21004 (2.66 Å) is shown by a dashed red line. c Representation of the PKS21004 (green sticks) in the β5i active site (purple cartoon). The structure of β5 (gray cartoon, PDB 5LF1) is superimposed for comparison. The right panel is an enlarged and rotated view of the area in the square box of the left panel. Red dots denote the active residue Thr1 of β5 and β5i. The two residues in human β5i that make contact with the inhibitor and are different from the human β5c are shown in stick and marked by two black arrows