COMPARISON OF INHIBITOR BINDING IN HIV-1 PROTEASE AND IN NONVIRAL ASPARTIC PROTEASES - THE ROLE OF THE FLAP

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. © 1990.