Human immunodeficiency virus type 1 protease and human immunodeficiency virus type 2 protease (HIV-1 PR and HIV-2 PR)

Human immunodeficiency virus type 1 protease and type 2 protease are essential retroviral aspartyl proteases encoded by the HIV-1 and HIV-2 genomes. These enzymes exist as homodimers of 99 amino acid subunits and possess a conserved Asp-Thr-Gly catalytic triad at the active site. Their principal biological function is to cleave newly synthesized Gag and Gag-Pol viral polyproteins at multiple sites, thus essential for the production of mature, infectious HIV virions and viral replication. Inhibitors of these proteases, called HIV protease inhibitors, are a central element of antiretroviral therapy. HIV-1 and HIV-2 PR differ in their sequence and specificity, and mutations can confer drug resistance, representing a clinical challenge. The inhibition of these proteases underlies a key therapeutic strategy for HIV/AIDS and is associated with specific long-term safety and metabolic concerns.

Other names

HIV-1 proteaseHIV-2 proteaseretropepsinviral aspartyl proteasePR (for protease)

Competitive inhibition of peptide bond hydrolysis in Gag and Gag-Pol polyproteins, prevention of viral particle maturation, and blockade of active site aspartyl protease activity.