HIV Protease

What is a Protease?

Proteases are basically proteins that break down other proteins. They cleave the peptide bonds that link amino acids together. Proteases also have many functions. Proteases such as pepsin and trypsin break down proteins in food so that it can be absorbed into the blood for further metabolism. Certain proteases destroy harmful proteins. For example white cells use these proteases to break down bacteria and parasites. There are also many biological and regulatory functions of the proteases.

Role of Protease in HIV

Since viruses are so small they must make maximum use of the minimal genetic information that they have. HIV does this by making a long polypeptide chains that contains many proteins. These protein precurser, Gag and Gag Pol must be cleaved by protease at 9 specific points in order to produce functional proteins. The gag precurser will eventually give rise to structural proteins and pol precurser will give rise to enzymes such as reverse transcriptase, integrase, and protease. Thus, an HIV specific protease is necessary for the the HIV to make more functional viruses. The HIV protease is not found in mammalian cells. The HIV protease is unique in that it can cleave between a phenylalanine and tyrosine or proline. To look at the reaction click here This is a very important fact because no human enzyme can cleave between either tyrosine or phenyalanine and proline. For more information on the genetics of HIV click here. The HIV Protease is an enzyme with two symmetrical subunits. The active site is located where the two subunits meet. HIV proteases are aspartic acid proteases and thus, aspartate 25 plays a key role in binding the substrate.

HIV Protease: Active Site

Reaction of the HIV Protease