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HIV-1 Protease
The homodimer structure consists of two identical polypeptides of 99 amino acids. HIV-1 protease cleaves Gag polyprotein that yields the active protein components of HIV.
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Secondary Structure
HIV-1 Protease contains alpha-helices, beta-sheets, and turns in both dimer units. One sheet is part of the quarternary structure since it contains alternating strands of chain A and chain B.
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Hydrophilic Interaction
Tertiary Structure

The polar residues on the outer edges of the homodimer provides hydrophilic interaction with the solvent water. Also shown here is an inhibitor bound to the active site of the protease.
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Inhibitor Structure
The inhibitor, or "I" chain, is a pseudopeptide containing five residues: napthyloxyacetyl (NOA 1) attached to the amino group of His, the carboxyl group of His bonded to the amino of 5-amino-6- cyclohexyl-3,4-dihydroxy- 2-isopropyl-hexanoyl acid (CAV 3), the amino group of Ile forms a peptide bond with the hexanoyl, and lastly 2-aminomethyl-pyridine forms a peptide bond with Ile. The two Asp (see Slides 8 & 9) are shown in spacefill.
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Another View
Pseudopeptide Inhibitor

The two subunits of the protease displayed as spacefill with the inhibitor shown as ball and stick, and the Asp at the active site colored cpk.
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Non-peptide Inhibitor
In this example, the inhibitor bound at the active site is a fluoro substitituted diol-based symmetrical hydrocarbon.
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Binding Site
The shaded surface of the inhibitor outlines the volume occupied by the substrate and shows the areas where the ligand contacts the homodimer - the fluorines are key areas of contact.
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Aspartic Protease
Looking solely at one domain, the HIV Protease has a strong similarity to aspartic proteases. The simple aspartic proteases only have a single active-site "flap" as shown here.
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Aspartic Protease
The active site at the interface of the homodimer consists of two "flaps" and two aspartate residues, Asp25 on each subunit as shown here.
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Protease Inhibitors Give Life to AIDS Patients
Recent discoveries of certain drugs have been shown to bind tightly to the active site of HIV Protease preventing the development of new virus particles. Four common drugs include: Crixivan, Invirase, Norvir, and Viracept. The OH-group backbone inserts between the two active site carboxyl groups of the protease and prevents protease activity. This slide shows the point of contact at the active site where the drugs would in fact bind. These drugs are especially successful because they do not have undesirable side effects - they have a focused purpose and do not impact other biological functions in the body.
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