6U7O
HIV-1 wild type protease with GRL-00819A, with phenyl-boronic-acid as P2'-ligand and with a 6-5-5-ring fused crown-like tetrahydropyranofuran as the P2-ligand
Summary for 6U7O
| Entry DOI | 10.2210/pdb6u7o/pdb |
| Related | 2IEN 4I8W 4I8Z 6BZ2 6C8X 6U7P |
| Descriptor | Protease, SODIUM ION, CHLORIDE ION, ... (7 entities in total) |
| Functional Keywords | aspartic acid protease, hiv-1 protease inhibitor of grl-00819a, boronic acid, viral protein |
| Biological source | Human immunodeficiency virus 1 |
| Total number of polymer chains | 2 |
| Total formula weight | 22386.78 |
| Authors | Wang, Y.-F.,Kneller, D.W.,Weber, I.T. (deposition date: 2019-09-03, release date: 2019-10-09, Last modification date: 2023-10-11) |
| Primary citation | Ghosh, A.K.,Xia, Z.,Kovela, S.,Robinson, W.L.,Johnson, M.E.,Kneller, D.W.,Wang, Y.F.,Aoki, M.,Takamatsu, Y.,Weber, I.T.,Mitsuya, H. Potent HIV-1 Protease Inhibitors Containing Carboxylic and Boronic Acids: Effect on Enzyme Inhibition and Antiviral Activity and Protein-Ligand X-ray Structural Studies. Chemmedchem, 14:1863-1872, 2019 Cited by PubMed Abstract: We report the synthesis and biological evaluation of phenylcarboxylic acid and phenylboronic acid containing HIV-1 protease inhibitors and their functional effect on enzyme inhibition and antiviral activity in MT-2 cell lines. Inhibitors bearing bis-THF ligand as P2 ligand and phenylcarboxylic acids and carboxamide as the P2' ligands, showed very potent HIV-1 protease inhibitory activity. However, carboxylic acid containing inhibitors showed very poor antiviral activity relative to carboxamide-derived inhibitors which showed good antiviral IC value. Boronic acid derived inhibitor with bis-THF as the P2 ligand showed very potent enzyme inhibitory activity, but it showed lower antiviral activity than darunavir in the same assay. Boronic acid containing inhibitor with a P2-Crn-THF ligand also showed potent enzyme K but significantly decreased antiviral activity. We have evaluated antiviral activity against a panel of highly drug-resistant HIV-1 variants. One of the inhibitors maintained good antiviral activity against HIV and HIV viruses. We have determined high resolution X-ray structures of two synthetic inhibitors bound to HIV-1 protease and obtained molecular insight into the ligand-binding site interactions. PubMed: 31549492DOI: 10.1002/cmdc.201900508 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.33 Å) |
Structure validation
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