User:David Canner/Sandbox HIV

spinqualitylabelsall models Structure of HIV Protease Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Human Immunodeficiency Virus is a notoriously lethal virus that is known to cause AIDS. It is a homodimeric protein made by the HIV virus that is crucial to the virus's infectious capacity. The virus makes certain proteins that need to be cleaved, in order to transform into mature, fully-functional proteins that can allow the virus to infect new cells. HIV-1 protease is responsible for cleaving these nascent proteins into their mature form.

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 tunnel appears to be rather narrow. 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. A

Medical Implications

There currently is no cure or vaccine against contracting HIV. Scientists 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 , thus preventing the protease from cleaving any protein chains. Y^[2]

Other drugs used to treat patients infected with the HIV virus include Indinavir (PDB entry 1hsg), Ritonavir (PDB entry 1hxw), and Nelfinavir (PDB entry 1ohr).