Hiv-1 Protease Complexed With A Macrocyclic Peptidomimetic Inhibitor

This structure shows the two chains of the protease of human immunodeficiency virus complexed to an inhibitor that mimics the region of the protein to be cleaved.

The macrocycles possess two amides and an aromatic group within 15-17 membered rings designed to replace N- or C-terminal tripeptides from peptidic inhibitors of HIV protease. These cyclic analogues are potent inhibitors of HIV protease, and the crystal structures show them to be structural mimics of acyclic peptides, binding in the active site of the protease via the same interactions. Each macrocycle is restrained to adopt a beta-strand conformation which is preorganized for protease binding. An unusual feature of the binding of C-terminal macrocyclic inhibitors is the interaction between a positively charged secondary amine and a catalytic aspartate of HIV protease

Use the buttons to highlight the individual chains of the protease or to see the inhibitor. Highlight the aspartate residues. You will see that each chain contains three aspartates, two of which  are involved in the catalytic process. This structure only three asparates interact with the inhibitor

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© Richard Hunt, University of South Carolina School of Medicine