 HIV-1 protease

HIV-1 protease is an aspartic protease of HIV-1. It catalyses peptide bond hydrolysis during viral maturation. The active enzyme is a protein dimer made from two identical subunits, each about $11\mathrm{kDa}$. Thus a single isolated subunit and the assembled catalytic enzyme are different molecular objects.^[ref]

Cleavage specificity depends on the amino-acid residues around the bond. In the nomenclature $P_1\mid P_1^{\prime }$, the vertical line marks the cleaved bond: $P_1$ is on one side and $P_1^{\prime }$ on the other. The enzyme favors a hydrophobic $P_1$ residue, while $P_1^{\prime }$ varies and is often proline.^[ref]

A short peptide assay can therefore test cleavage of one specified sequence, but its result is conditional on that substrate and the assay conditions. Measuring disappearance of the uncleaved peptide or appearance of a cleavage product addresses chemical processing directly. It differs from measuring the number of viral particles, which additionally depends on many other steps. The enzyme's role in maturation explains why inhibiting its activity can disrupt that process and why it is an antiviral drug target.^[ref]