Structure
Indinavir is an antiviral compound that acts as a protease inhibiter. Figure 2 below depicts Indinavir’s structure. The drug has a molecular weight of 711.875 g/mol and is very soluble in water and ethanol [1]. Indinavir works by specifically binding to the HIV-1 protease active site by mimicking a target substrate protein and essentially becoming “stuck” in the enzyme active site, disabling the enzyme. Indinavir’s pyridine attracts protease Arg8 to hold it in place. Its ketone interacts with the protease Asp25 to perform initiate aspartic catalysis. The bond between the ketone and amine doesn't lyse due to the nature of the inhibitor.
Function
Mechanism
The active site of HIV-1 protease is inhibited by Indinavir when the molecule interacts with the specific sites that a viral protein normally would interact with. The active site contains Asp25, which is involved in peptide cleavage, Thr26, which is involved in stabilizing the active site conformation, and Gly27, which is involved in the binding of a protein in a position that gives Asp25 access to its cleavage site. (Don't know how to reference this) Arg8 also plays a role in holding a substrate in place in the enzyme active site. When the Indinavir molecule enters the protease active site it imitates the specific protein. I wrote something but can't remember what it was.
Indinavir acts with the Asp25, Thr26 and Gly27 subunits in the HIV-1 protease enzyme.[2]
Cellular Effects
Indinavir blocks the cleavage of gag and gag-pol proteins. This inhibition does not allow for the maturation of new viral particles produced from infected cells. Viral particles that do not mature will not be able to infect new cells, lowering the viral load. Protease inhibitors do not have any effect on already infected cells but they do prevent further cell to cell transmission of the virus.
