3H5B
Crystal structure of wild type HIV-1 protease with novel P1'-ligand GRL-02031
Summary for 3H5B
| Entry DOI | 10.2210/pdb3h5b/pdb |
| Related | 2HB3 2IEN 2Z4O 3DJK 3DK1 |
| Descriptor | HIV-1 protease, SODIUM ION, CHLORIDE ION, ... (6 entities in total) |
| Functional Keywords | hiv-1, wild type protease, protease inhibitor, p1'-ligand, aids, hydrolase |
| Biological source | Human immunodeficiency virus type 1 (BRU ISOLATE) (HIV-1) |
| Cellular location | Gag-Pol polyprotein: Host cell membrane ; Lipid-anchor. Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P03367 |
| Total number of polymer chains | 2 |
| Total formula weight | 22269.06 |
| Authors | Tie, Y.,Wang, Y.F.,Weber, I.T. (deposition date: 2009-04-21, release date: 2009-06-16, Last modification date: 2023-09-06) |
| Primary citation | Ghosh, A.K.,Leshchenko-Yashchuk, S.,Anderson, D.D.,Baldridge, A.,Noetzel, M.,Miller, H.B.,Tie, Y.,Wang, Y.F.,Koh, Y.,Weber, I.T.,Mitsuya, H. Design of HIV-1 protease inhibitors with pyrrolidinones and oxazolidinones as novel P1'-ligands to enhance backbone-binding interactions with protease: synthesis, biological evaluation, and protein-ligand X-ray studies. J.Med.Chem., 52:3902-3914, 2009 Cited by PubMed Abstract: Structure-based design, synthesis, and biological evaluation of a series of novel HIV-1 protease inhibitors are described. In an effort to enhance interactions with protease backbone atoms, we have incorporated stereochemically defined methyl-2-pyrrolidinone and methyl oxazolidinone as the P1'-ligands. These ligands are designed to interact with Gly-27' carbonyl and Arg-8 side chain in the S1'-subsite of the HIV protease. We have investigated the potential of these ligands in combination with our previously developed bis-tetrahydrofuran (bis-THF) and cyclopentanyltetrahydrofuran (Cp-THF) as the P2-ligands. Inhibitor 19b with a (R)-aminomethyl-2-pyrrolidinone and a Cp-THF was shown to be the most potent compound. This inhibitor maintained near full potency against multi-PI-resistant clinical HIV-1 variants. A high resolution protein-ligand X-ray crystal structure of 19b-bound HIV-1 protease revealed that the P1'-pyrrolidinone heterocycle and the P2-Cp-ligand are involved in several critical interactions with the backbone atoms in the S1' and S2 subsites of HIV-1 protease. PubMed: 19473017DOI: 10.1021/jm900303m PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.29 Å) |
Structure validation
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