6V4T
MPER-TMD of HIV-1 Env bound with the entry inhibitor S2C3
Summary for 6V4T
| Entry DOI | 10.2210/pdb6v4t/pdb |
| Related | 6E8W |
| NMR Information | BMRB: 30503 |
| Descriptor | Envelope glycoprotein gp160, 4,4'-(decane-1,10-diyl)bis(9-amino-2,3-dihydro-1H-cyclopenta[b]quinolin-4-ium) (2 entities in total) |
| Functional Keywords | hiv-1 env, small-molecule, entry inhibitor, mper, viral protein |
| Biological source | Human immunodeficiency virus 1 |
| Total number of polymer chains | 3 |
| Total formula weight | 20064.34 |
| Authors | Xiao, T.,Frey, G.,Fu, Q.,Lavine, C.L.,Scott, D.A.,Seaman, M.S.,Chou, J.J.,Chen, B. (deposition date: 2019-11-30, release date: 2020-04-01, Last modification date: 2024-05-15) |
| Primary citation | Xiao, T.,Frey, G.,Fu, Q.,Lavine, C.L.,Scott, D.A.,Seaman, M.S.,Chou, J.J.,Chen, B. HIV-1 fusion inhibitors targeting the membrane-proximal external region of Env spikes. Nat.Chem.Biol., 16:529-537, 2020 Cited by PubMed Abstract: Combination antiretroviral therapy has transformed HIV-1 infection, once a fatal illness, into a manageable chronic condition. Drug resistance, severe side effects and treatment noncompliance bring challenges to combination antiretroviral therapy implementation in clinical settings and indicate the need for additional molecular targets. Here, we have identified several small-molecule fusion inhibitors, guided by a neutralizing antibody, against an extensively studied vaccine target-the membrane proximal external region (MPER) of the HIV-1 envelope spike. These compounds specifically inhibit the HIV-1 envelope-mediated membrane fusion by blocking CD4-induced conformational changes. An NMR structure of one compound complexed with a trimeric MPER construct reveals that the compound partially inserts into a hydrophobic pocket formed exclusively by the MPER residues, thereby stabilizing its prefusion conformation. These results suggest that the MPER is a potential therapeutic target for developing fusion inhibitors and that strategies employing an antibody-guided search for novel therapeutics may be applied to other human diseases. PubMed: 32152540DOI: 10.1038/s41589-020-0496-y PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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