3TOG
HIV-1 Protease - Epoxydic Inhibitor Complex (pH 9 - Monoclinic Crystal form P21)
Summary for 3TOG
| Entry DOI | 10.2210/pdb3tog/pdb |
| Related PRD ID | PRD_001019 |
| Descriptor | Gag-Pol polyprotein, DIMETHYL SULFOXIDE, (S)-N-((2S,3S,4R,5R)-4-amino-3,5-dihydroxy-1,6-diphenylhexan-2-yl)-3-methyl-2-(2-phenoxyacetamido)butanamide, ... (4 entities in total) |
| Functional Keywords | hiv pr, epoxide, in-crystal reaction, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Human immunodeficiency virus type 1 (BRU ISOLATE) (HIV-1) |
| Total number of polymer chains | 4 |
| Total formula weight | 44264.42 |
| Authors | Geremia, S.,Olajuyigbe, F.M.,Demitri, N. (deposition date: 2011-09-05, release date: 2012-08-15, Last modification date: 2023-09-13) |
| Primary citation | Olajuyigbe, F.M.,Demitri, N.,De Zorzi, R.,Geremia, S. Developing HIV-1 Protease Inhibitors through Stereospecific Reactions in Protein Crystals. Molecules, 21:-, 2016 Cited by PubMed Abstract: Protease inhibitors are key components in the chemotherapy of HIV infection. However, the appearance of viral mutants routinely compromises their clinical efficacy, creating a constant need for new and more potent inhibitors. Recently, a new class of epoxide-based inhibitors of HIV-1 protease was investigated and the configuration of the epoxide carbons was demonstrated to play a crucial role in determining the binding affinity. Here we report the comparison between three crystal structures at near-atomic resolution of HIV-1 protease in complex with the epoxide-based inhibitor, revealing an in-situ epoxide ring opening triggered by a pH change in the mother solution of the crystal. Increased pH in the crystal allows a stereospecific nucleophile attack of an ammonia molecule onto an epoxide carbon, with formation of a new inhibitor containing amino-alcohol functions. The described experiments open a pathway for the development of new stereospecific protease inhibitors from a reactive lead compound. PubMed: 27809253DOI: 10.3390/molecules21111458 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.24 Å) |
Structure validation
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