ABSTRACT
Since the discovery of human immunodeficiency virus (HIV) as the causative agent of acquired immunodeficiency syndrome (AIDS), perhaps the largest and most powerful consortium of scientists ever assembled to tackle a single disease has been brought to bear on the problem of AIDS and its treatment. Retroviral proteases such as HIV protease (PR) are the latest additions to the well-studied family of aspartic proteases. Determination of the crystal structures of HIV PR gave new impetus to the design of novel inhibitors. The crystal structures of HIV PR confirmed the predicted dimeric character of the enzyme. In the structure of the apo-form of HIV PR, the flaps from both monomers are related by crystallographic two-fold symmetry and can he considered as being in an open conformation. The crystal structure of compound IV or AG1284 complexed with HIV type 1 PR was solved, revealing excellent complementarity between the ligand and protein.
