Several investigators have suggested that the HIV virus entered the human population by crossing from our nearest evolutionary neighbors, the great apes.

The structure and sequence of the simian protease certainly accord with this: structures superpose with rmsd of only 0.44 A, and the two have 92% sequence identity:

Structural Comparison of Human (1hiv) and Simian (1ytg) HIV Proteases
Asp25 and 25' shown as CPK Models

Sequence Alignment of Human (1hiv) and Simian (1ytg) HIV Proteases

The mutation rate referred to on the previous page would certianly allow the simian and human proteins to diverge rapidly.

Every structure for HIV-1 protease in the Protein DataBank, and in the new HIV Protease DataBank is that of an inhibited enzyme, indicating the major activity in finding a way to stop the protease.

Here is one example:

Human HIV-1 Protease Bound to Inhibitor L-735,524 (1hsh)	Closeup of Catalytic Site

The inhibitor bound here has the advantage of being orally usable:

Another evidence of the rapid mutation rate:

• The difference between HIV-1 protease, the predominant variety in North America and Europe and HIV-2 protease, the variety found in West Africa, is greater than the difference between HIV-1 and SIV!

Structure Alignment of HIV-1 (1hiv) and HIV-2 (1hsh)
Backbone rmsd = 0.96 A; Asp25,25' as CPK Models

The sequence alignment is 48% identity and 68% similarity:

Sequence Alignment of HIV-1 (1hiv) and HIV-2 (1hsh)

As usual, the residues in the vicinity of the catalytic site are strongly conserved.