Comparison of inhibitor binding in HIV‐1 protease and in non‐viral aspartic proteases: the role of the flap

Abstract

The crystal structure of HIV‐1 protease with an inhibitor has been compared with the structures of non‐viral aspartic proteases complexed with inhibitors. In the dimeric HIV‐1 protease, two 4‐stranded β‐sheets are formed by half of the inhibitor, residues 27–29, and the flap from each monomer. In the monomeric non‐viral enzyme the single flap does not form a β‐sheet with an inhibitor. The HIV‐1 protease shows more interactions with a longer peptide inhibitor than are observed in non‐viral aspartic protease‐inhibitor complexes. This, and the large movement of the flaps, restricts the conformation of the protease cleavage sites in the retroviral polyprotein precursor.