Virtuelle (Nano) Welten: PDB Molecule of the Month 6: HIV Protease

A Small But Effective Enzyme

HIV-1 protease is a small enzyme, composed of two identical protein chains, each only 99 amino acids long. The two chains assemble to form a long tunnel, seen here from the side, covered by two flexible protein "flaps." The flaps open up and the enzyme wraps around a protein chain, closing and holding it tightly in the tunnel.

The active site is at the center of the tunnel, where a water molecule is used to break the protein chain. This illustration shows the enzyme from the top (the PDB accession code for this structure is 7hvp). In the two illustrations on the right, the flaps have been removed to show the active site. The center illustration shows the location of an inhibitor (green) which is similar to the position occupied by a protein chain. (There are no structures of a protein bound to the active form of HIV-1 protease, because the chain would be cleaved before the structure could be solved! So, we need to look at how inhibitors bind to imagine how the enzyme binds to protein chains.) Notice how the inhibitor chain is stretched straight through the active site. In the right illustration, the inhibitor has been removed so that we can see the active site. Two aspartate amino acids, shown with asterisks, do all of the work, attacking the protein chain at the very middle.