A distinct binding mode of a hydroxyethylamine isostere inhibitor of HIV-1protease

Crystallization conditions for an HIV-1 protease-inhibitor complex were opt imized to produce crystals suitable for X-ray diffraction experiments. The X-ray structure of the HIV-1 protease complex was solved and refined at 3.1 Angstrom resolution. In contrast to Saquinavir, the mimetic hydroxy group of the inhibitor Boc-Phe-Psi[(S)-CH(OH)CH2-NH]-Phe-Glu-Phe-NH2 is placed as ymmetrically with respect to the non-crystallographic twofold axis of the p rotease dimer so that hydrogen bonds between the amino group of the inhibit or and the catalytic aspartates can be formed. The inhibitor binds in the c entre of the active site by a compact network of hydrogen bonds to Gly27, G ly127, Asp25, Asp125 and via the buried water molecule W301 to Ile50 and Il e150.