9EEE
Room-temperature X-ray structure of HIV-1 protease in complex with GRL-10624A inhibitor
This is a non-PDB format compatible entry.
Summary for 9EEE
| Entry DOI | 10.2210/pdb9eee/pdb |
| Descriptor | Protease, (3S,3aS,4S,7R,8aS)-3-methylhexahydro-1H,3H-3a,7-epoxycyclohepta[c]furan-4-yl {(2S,3R)-3-hydroxy-4-[(4-methoxybenzene-1-sulfonyl)(2-methylpropyl)amino]-1-phenylbutan-2-yl}carbamate, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | hiv-1 protease, homodimer, inhibitor complex, hydrolase-inhibitor complex, hydrolase/inhibitor |
| Biological source | Human immunodeficiency virus 1 |
| Total number of polymer chains | 2 |
| Total formula weight | 22169.02 |
| Authors | Kovalevsky, A.,Gerlits, O.,Ghosh, A. (deposition date: 2024-11-19, release date: 2025-02-05, Last modification date: 2025-02-12) |
| Primary citation | Ghosh, A.K.,Yadav, M.,Sharma, A.,Johnson, M.,Ghosh, A.K.,Prasad, R.,Amano, M.,Gerlits, O.,Kovalevsky, A.,Mitsuya, H. Potent HIV‐1 protease inhibitors containing oxabicyclo octanol-derived P2-ligands: Design, synthesis, and X‐ray structural studies of inhibitor-HIV-1 protease complexes. Bioorg.Med.Chem.Lett., 120:130109-130109, 2025 Cited by PubMed Abstract: We describe here the design, synthesis, and X-ray structural studies of a new class of HIV-1 protease inhibitors containing 8-oxabicyclo[3.2.1]octanol-derived P2 ligands. We investigated the functional effect of these stereochemically defined fused-poly cyclic ligands on enzyme inhibition and antiviral activity in MT-2 cells. The tricyclic core of 8-oxabicyclo[3.2.1]octan-6-ol is designed to interact with the residues in the S2 subsite of HIV-1 protease. The syntheses of the ligands were carried out using the [5+2]-cycloaddition as the key step. Several inhibitors exhibited potent enzyme inhibitory activity. High resolution room-temperature X-ray structures of inhibitor-bound HIV-1 protease were determined. These structures provided important molecular insights for further design and optimization of inhibitor potency. PubMed: 39848476DOI: 10.1016/j.bmcl.2025.130109 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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