Conformation of 12X FIV protease in complex with the inhibitor TL-3. The hydrogen bonding network between TL-3 and 12X FIV protease is formed predominantly by main chain atoms of residues in the catalytic loop (residues 30–34) and flap regions (residues G57, I59) of the protease. The network is mediated by five ordered water molecules (W1–W3, W1'–W2'). This hydrogen bonding network is essentially identical to that formed by TL-3 in the active sites of both wild-type HIV and FIV protease [11, 12, 13, 26]. The equivalent residue numbers for HIV protease are indicated in superscript.