8ESY
D30N mutant HIV protease in complex with benzoxaborolone analog of darunavir
Summary for 8ESY
| Entry DOI | 10.2210/pdb8esy/pdb |
| Descriptor | Protease, GLYCEROL, CHLORIDE ION, ... (5 entities in total) |
| Functional Keywords | virus, protease, inhibitor, boron, hydrolase, hydrolase-inhibitor complex, hydrolase/inhibitor |
| Biological source | Human immunodeficiency virus 1 |
| Total number of polymer chains | 2 |
| Total formula weight | 22297.30 |
| Authors | Windsor, I.W.,Graham, B.J.,Raines, R.T. (deposition date: 2022-10-15, release date: 2023-02-08, Last modification date: 2023-10-25) |
| Primary citation | Graham, B.J.,Windsor, I.W.,Raines, R.T. Inhibition of HIV-1 Protease by a Boronic Acid with High Oxidative Stability. Acs Med.Chem.Lett., 14:171-175, 2023 Cited by PubMed Abstract: HIV-1 protease is an important target for pharmaceutical intervention in HIV infection. Extensive structure-based drug design led to darunavir becoming a key chemotherapeutic agent. We replaced the aniline group of darunavir with a benzoxaborolone to form BOL-darunavir. This analogue has the same potency as darunavir as an inhibitor of catalysis by wild-type HIV-1 protease and, unlike darunavir, does not lose potency as an inhibitor of the common D30N variant. Moreover, BOL-darunavir is much more stable to oxidation than is a simple phenylboronic acid analogue of darunavir. X-ray crystallography revealed an extensive network of hydrogen bonds between the enzyme and benzoxaborolone moiety, including a novel direct hydrogen bond from a main-chain nitrogen to the carbonyl oxygen of the benzoxaborolone moiety that displaces a water molecule. These data highlight the utility of benzoxaborolone as a pharmacophore. PubMed: 36793428DOI: 10.1021/acsmedchemlett.2c00464 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.35 Å) |
Structure validation
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