4KB9
Crystal structure of wild-type HIV-1 protease with novel tricyclic P2-ligands GRL-0739A
Summary for 4KB9
| Entry DOI | 10.2210/pdb4kb9/pdb |
| Related | 2IEN 3OK9 |
| Descriptor | Protease, (3aR,3bR,4S,7aR,8aS)-decahydrofuro[2,3-b][1]benzofuran-4-yl [(2S,3R)-3-hydroxy-4-{[(4-methoxyphenyl)sulfonyl](2-methylpropyl)amino}-1-phenylbutan-2-yl]carbamate, CHLORIDE ION, ... (7 entities in total) |
| Functional Keywords | spartic acid protease, hiv-1 protease inhibitor grl-0739a, a novel tricyclic p2-ligand, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Human immunodeficiency virus 1 |
| Total number of polymer chains | 2 |
| Total formula weight | 22553.33 |
| Authors | Wang, Y.-F.,Agniswamy, J.,Weber, I.T. (deposition date: 2013-04-23, release date: 2013-09-04, Last modification date: 2023-09-20) |
| Primary citation | Ghosh, A.K.,Parham, G.L.,Martyr, C.D.,Nyalapatla, P.R.,Osswald, H.L.,Agniswamy, J.,Wang, Y.F.,Amano, M.,Weber, I.T.,Mitsuya, H. Highly Potent HIV-1 Protease Inhibitors with Novel Tricyclic P2 Ligands: Design, Synthesis, and Protein-Ligand X-ray Studies. J.Med.Chem., 56:6792-6802, 2013 Cited by PubMed Abstract: The design, synthesis, and biological evaluation of a series of HIV-1 protease inhibitors incorporating stereochemically defined fused tricyclic P2 ligands are described. Various substituent effects were investigated to maximize the ligand-binding site interactions in the protease active site. Inhibitors 16a and 16f showed excellent enzyme inhibitory and antiviral activity, although the incorporation of sulfone functionality resulted in a decrease in potency. Both inhibitors 16a and 16f maintained activity against a panel of multidrug resistant HIV-1 variants. A high-resolution X-ray crystal structure of 16a-bound HIV-1 protease revealed important molecular insights into the ligand-binding site interactions, which may account for the inhibitor's potent antiviral activity and excellent resistance profiles. PubMed: 23947685DOI: 10.1021/jm400768f PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.29 Å) |
Structure validation
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