HIV-1 Protease is a viral enzyme in HIV that cleaves longer proteins into the enzymes, coreproteins, and glycoproteins of the virus. The Protease is made up two subunits, thus it is a homodimer. It is made up of mostly Beta Sheets and a pair of small Alpha Helices. When viral polypeptides go in, the tunnel appears too small to admit them, but Protease undergoes comformational changes to allow them. The flaps, the top part, move up and the flaps move down again for the active site to facilitate the peptide cleavage.
Protease plays a big role in viral replication. Inhibition of this enzyme can stop replication. Most inhibitors of the Protease end in "navir".
Peptidic Protease InhibitorsEdit
PPI's are Protease Inhibitors look like a typical peptide chain. These types of inhibitors bind to the amino acids of the Protease with hydrogen bonds, and blocks the active sit of the Protease. Mutations in the Protease however, can lead to resistance or even cross resistance to these inhibitors.
Non Peptidic Protease InhibitorsEdit
Non Peptidic Protease Inhibitors such as Tipranavir bind differently. Some amino acids in the Protease are important for the active site to work. They are always the same. If those amino acids are mutated, the enzyme will lose its function. Non Peptidic Protease Inhibitors bind to these elements, with hydrogen bonds. At the top of the Protease, Isoleucine 50 amino acids are located. These are one of the conserved amino acids. Some Protease Inhibitors bind indirectly to these elements with a water molecule. Mutations eventually weaken the hydrogen bonds of these Protease Inhibitors. Other inhibitors such as Tipranavir bind to them directly. Non Peptidic Protease Inhibitors have comformational activity. Tipranavir performs these activities more frequently than other inhibitors.