2HB3
Wild-type HIV-1 Protease in complex with potent inhibitor GRL06579
Summary for 2HB3
| Entry DOI | 10.2210/pdb2hb3/pdb |
| Descriptor | Protease, CHLORIDE ION, SODIUM ION, ... (6 entities in total) |
| Functional Keywords | active-site cavity protease inhibitor catalytic aspartic acid, hydrolase |
| Biological source | Human immunodeficiency virus 1 |
| Cellular location | Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P03366 |
| Total number of polymer chains | 2 |
| Total formula weight | 22286.49 |
| Authors | Kovalevsky, A.Y.,Weber, I.T. (deposition date: 2006-06-13, release date: 2006-08-29, Last modification date: 2024-02-14) |
| Primary citation | Ghosh, A.K.,Sridhar, P.R.,Leshchenko, S.,Hussain, A.K.,Li, J.,Kovalevsky, A.Y.,Walters, D.E.,Wedekind, J.E.,Grum-Tokars, V.,Das, D.,Koh, Y.,Maeda, K.,Gatanaga, H.,Weber, I.T.,Mitsuya, H. Structure-Based Design of Novel HIV-1 Protease Inhibitors To Combat Drug Resistance. J.Med.Chem., 49:5252-5261, 2006 Cited by PubMed Abstract: Structure-based design and synthesis of novel HIV protease inhibitors are described. The inhibitors are designed specifically to interact with the backbone of HIV protease active site to combat drug resistance. Inhibitor 3 has exhibited exceedingly potent enzyme inhibitory and antiviral potency. Furthermore, this inhibitor maintains impressive potency against a wide spectrum of HIV including a variety of multi-PI-resistant clinical strains. The inhibitors incorporated a stereochemically defined 5-hexahydrocyclopenta[b]furanyl urethane as the P2-ligand into the (R)-(hydroxyethylamino)sulfonamide isostere. Optically active (3aS,5R,6aR)-5-hydroxy-hexahydrocyclopenta[b]furan was prepared by an enzymatic asymmetrization of meso-diacetate with acetyl cholinesterase, radical cyclization, and Lewis acid-catalyzed anomeric reduction as the key steps. A protein-ligand X-ray crystal structure of inhibitor 3-bound HIV-1 protease (1.35 A resolution) revealed extensive interactions in the HIV protease active site including strong hydrogen bonding interactions with the backbone. This design strategy may lead to novel inhibitors that can combat drug resistance. PubMed: 16913714DOI: 10.1021/jm060561m PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.35 Å) |
Structure validation
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