Comparison of superimposed crystal structures of ligand-protease complexes (proteases not shown) for HIV-1 protease and P. falciparum plasmepsin II. (Top) Superimposition of crystal structures for HIV protease inhibitor complexes showing protease-bound ligand conformations: lopinavir (PDB code, 1mui), indinavir (1hsg), ritonavir (1hxw), amprenavir (1hpv), saquinavir (1hxb), nelfinavir (1ohr), BR124 (1d4l), BR314 (1d4k). Overlay was performed using backbone atoms N, Cα, and C (or equivalent) from P2-P1′ using the Search and Compare module within InsightII. (Middle) Superimposition of crystal structures for P. falciparum PM-II inhibitor complexes showing protease-bound conformations: pepstatin A (1m43), pepstatin A (1sme), statine-based ligand (1me6), rs367 (1lee), rs370 (1lf2), EH58 (1lf3). Overlay was performed using backbone atoms N, Cα, and C (or equivalent) from P3-P1′. (Bottom) Superimposition of above enzyme-bound HIV-1 protease inhibitors (black) on PfPM-II inhibitors (gray) using backbone atoms N, Cα, and C (or equivalent) from P2-P1′.