Comparison of inhibitor binding in HIV-1 protease and in non-viral aspartic proteases: the role of the flap.
The crystal structure of HIV-1 protease with an inhibitor has been compared with the structures of non-viral aspartic proteases complexed with inhibitors. In the dimeric HIV-1 protease, two 4-stranded beta-sheets are formed by half of the inhibitor, residues 27-29, and the flap from each monomer. In the monomeric non-viral enzyme the single flap does not form a beta-sheet with an inhibitor. The HIV-1 protease shows more interactions with a longer peptide inhibitor than are observed in non-viral aspartic protease-inhibitor complexes. This, and the large movement of the flaps, restricts the conformation of the protease cleavage sites in the retroviral polyprotein precursor.
Gustchina
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Crystallography Laboratory, NCI-Frederick Cancer Research and Development Center, MD 21701.
Weber
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D016282:Aspartic Acid Endopeptidases; D001665:Binding Sites; D003461:Crystallography; D010450:Endopeptidases; D015684:Gene Products, pol; D006678:HIV / Q000201:enzymology*; D016333:HIV Protease; D006860:Hydrogen Bonding; D046911:Macromolecular Substances; D008958:Models, Molecular; D009038:Motion; D011480:Protease Inhibitors; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D015684:Gene Products, pol; D046911:Macromolecular Substances; D011480:Protease Inhibitors; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; D016333:HIV Protease; C035794:rhizopuspepsin