Comparison of inhibitor binding in HIV-1 protease and in non-viral aspartic proteases: the role of the flap |
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Authors: | A Gustchina I T Weber |
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Institution: | Crystallography Laboratory, NCI-Frederick Cancer Research and Development Center, MD 21701. |
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Abstract: | 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. |
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