HIV-Protease

Structure of HIV-1 Protease

Looking at the structure of HIV-1 protease, we see that the protein is composed of , each consisting of identical 99 amino acid chains. The subunits come together in such as way as to . This tunnel is of critical importance as it is the location where nascent proteins are bound before cleavage. In the middle of the tunnel is the active site of the protease:. The two Asp's act as in the active site and use a water molecule to help break the protein chain that binds in the tunnel. ^[1] You may be wondering how a protein to be cleaved makes its way into the active-site tunnel, as the. The key is the two flexible flaps on the top of the tunnel that can to enter the tunnel. The flaps , shifting from an open to closed conformation to securly binding its target in an appropriate conformation for cleavage.

Medical Implications

There currently is no cure or vaccine against contracting HIV. AIDS researchers, however, have discovered treatments that can slow progression of the HIV virus, thanks in large part to our understanding of the structure of HIV-1 protease. was the the first protease inhibitor approved by the FDA for the treatment of HIV. It inhibits HIV-1 protease by , preventing nascent peptides from entering and .^[2] Saquinavir effectively acts like an uncleavable ligand, highlighted by the protease flaps undergoing upon binding. Other drugs used to treat patients infected with the HIV virus which inhibit include (1hsg), (1hxw), and (1ohr).