9ON9
Immature HIV-1 CACTD-SP1 lattice with Maturation inhibitor PF-46396 (R) and Inositol hexakisphosphate (IP6)
This is a non-PDB format compatible entry.
Summary for 9ON9
| Entry DOI | 10.2210/pdb9on9/pdb |
| NMR Information | BMRB: 31246 |
| Descriptor | Capsid protein p24, 1-{(2R)-2-(4-tert-butylphenyl)-2-[(2,3-dihydro-1H-inden-2-yl)amino]ethyl}-3-(trifluoromethyl)pyridin-2(1H)-one, INOSITOL HEXAKISPHOSPHATE (3 entities in total) |
| Functional Keywords | hiv-1, maturation inhibitors, pf-46396, protein binding |
| Biological source | Human immunodeficiency virus type 1 (NEW YORK-5 ISOLATE) |
| Total number of polymer chains | 6 |
| Total formula weight | 67682.59 |
| Authors | Zadorozhnyi, R.,Quinn, C.M.,Zadrozny, K.K.,Ablan, S.D.,Kennedy, B.J.,Yap, G.P.A.,Sanner, D.,Kraml, C.,Freed, E.O.,Ganser-Pornillos, B.K.,Pornillos, O.,Gronenborn, A.M.,Polenova, T. (deposition date: 2025-05-14, release date: 2025-10-08) |
| Primary citation | Zadorozhnyi, R.,Quinn, C.M.,Zadrozny, K.K.,Ablan, S.D.,Kennedy, B.J.,Yap, G.P.A.,Sanner, D.,Kraml, C.,Freed, E.O.,Ganser-Pornillos, B.K.,Pornillos, O.,Gronenborn, A.M.,Polenova, T. Structural Basis for HIV-1 Maturation Inhibition by PF-46396 Determined by MAS NMR. J.Am.Chem.Soc., 147:34487-34497, 2025 Cited by PubMed Abstract: Among the different types of HIV-1 maturation inhibitors, those that stabilize the junction between the capsid protein C-terminal domain (CA) and the spacer peptide 1 (SP1) within the immature Gag lattice are promising candidates for antiretroviral therapies. Here, we report the atomic-resolution structure of CA-SP1 assemblies with the small-molecule maturation inhibitor PF-46396 and the assembly cofactor inositol hexakisphosphate (IP6), determined by magic angle spinning (MAS) NMR spectroscopy. Our results reveal that although the two PF-46396 enantiomers exhibit distinct binding modes, they both possess similar anti-HIV potency. PF-46396 binding arrests IP6 dynamics in the six-helix bundle pore, and the two enantiomers induce unique IP6 orientations in the pore. Importantly, our data suggest the presence of monoanionic IP6 form in the complex. Our study establishes the structural basis for PF-46396 action and suggests a mechanistic model for drug resistance. PubMed: 40924873DOI: 10.1021/jacs.5c08455 PDB entries with the same primary citation |
| Experimental method | SOLID-STATE NMR |
Structure validation
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