Summary for 3OXC
| Entry DOI | 10.2210/pdb3oxc/pdb |
| Related | 2IEN 2NMY 2NMZ 2NNK 2NNP 3CYX 3D1X 3D1Y 3MWS 3NU3 |
| Related PRD ID | PRD_000454 |
| Descriptor | Protease, (2S)-N-[(2S,3R)-4-[(2S,3S,4aS,8aS)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinolin-2-yl]-3-hydroxy-1 -phenyl-butan-2-yl]-2-(quinolin-2-ylcarbonylamino)butanediamide, FORMIC ACID, ... (5 entities in total) |
| Functional Keywords | enzyme inhibition, aspartic protease, hiv/aids, saquinavir, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Human immunodeficiency virus 1 |
| Total number of polymer chains | 2 |
| Total formula weight | 22436.37 |
| Authors | Kovalevsky, A.Y.,Wang, Y.-F.,Tie, Y.,Weber, I.T. (deposition date: 2010-09-21, release date: 2010-11-10, Last modification date: 2023-09-06) |
| Primary citation | Kovalevsky, A.Y.,Wang, Y.-F.,Tie, Y.,Weber, I.T. Atomic resolution crystal structures of HIV-1 protease and mutants V82A and I84V with saquinavir Proteins, 67:232-242, 2007 Cited by PubMed Abstract: Saquinavir (SQV), the first antiviral HIV-1 protease (PR) inhibitor approved for AIDS therapy, has been studied in complexes with PR and the variants PR(I) (84V) and PR(V) (82A) containing the single mutations I84V and V82A that provide resistance to all the clinical inhibitors. Atomic resolution crystal structures (0.97-1.25 A) of the SQV complexes were analyzed in comparison to the protease complexes with darunavir, a new drug that targets resistant HIV, in order to understand the molecular basis of drug resistance. PR(I) (84V) and PR(V) (82A) complexes were obtained in both the space groups P2(1)2(1)2 and P2(1)2(1)2(1), which provided experimental limits for the conformational flexibility. The SQV interactions with PR were very similar in the mutant complexes, consistent with the similar inhibition constants. The mutation from bigger to smaller amino acids allows more space to accommodate the large group at P1' of SQV, unlike the reduced interactions observed in darunavir complexes. The residues 79-82 have adjusted to accommodate the large hydrophobic groups of SQV, suggesting that these residues are intrinsically flexible and their conformation depends more on the nature of the inhibitor than on the mutations in this region. This analysis will assist with development of more effective antiviral inhibitors. PubMed: 17243183PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.16 Å) |
Structure validation
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