Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	A Strain-Specific Inhibitor of Receptor-Bound HIV-1 Targets a Pocket near the Fusion Peptide.
Journal, issue, pages	Cell Rep, Vol. 33, Issue 8, Page 108428, Year 2020
Publish date	Nov 24, 2020
Authors	Gabriel Ozorowski / Jonathan L Torres / Diogo Santos-Martins / Stefano Forli / Andrew B Ward /
PubMed Abstract	Disruption of viral fusion represents a viable, albeit under-explored, target for HIV therapeutics. Here, while studying the receptor-bound envelope glycoprotein conformation by cryoelectron ...Disruption of viral fusion represents a viable, albeit under-explored, target for HIV therapeutics. Here, while studying the receptor-bound envelope glycoprotein conformation by cryoelectron microscopy (cryo-EM), we identify a pocket near the base of the trimer containing a bound detergent molecule and perform in silico drug screening by using a library of drug-like and commercially available molecules. After down-selection, we solve cryo-EM structures that validate the binding of two small molecule hits in very similar manners to the predicted binding poses, including interactions with aromatic residues within the fusion peptide. One of the molecules demonstrates low micromolar inhibition of the autologous virus by using a very rare phenylalanine in the fusion peptide and stabilizing the surrounding region. This work demonstrates that small molecules can target the fusion process, providing an additional target for anti-HIV therapeutics, and highlights the need to explore how fusion peptide sequence variations affect receptor-mediated conformational states across diverse HIV strains.
External links	Cell Rep / PubMed:33238117 / PubMed Central
Methods	EM (single particle)
Resolution	3.5 - 4.04 Å
Structure data	20150 6opn EMDB-20150, PDB-6opn: CD4- and 17-bound HIV-1 Env B41 SOSIP in complex with small molecule GO35 Method: EM (single particle) / Resolution: 3.5 Å 20151 6opo EMDB-20151: C3 symmetry reconstruction of CD4- and 17-bound B41 HIV-1 Env SOSIP in complex with DDM PDB-6opo: Symmetric model of CD4- and 17-bound B41 HIV-1 Env SOSIP in complex with DDM Method: EM (single particle) / Resolution: 3.5 Å 20152 6opp EMDB-20152: Asymmetric reconstruction of CD4- and 17-bound B41 HIV-1 Env SOSIP in complex with DDM PDB-6opp: Asymmetric model of CD4- and 17-bound B41 HIV-1 Env SOSIP in complex with DDM Method: EM (single particle) / Resolution: 3.7 Å 20153 6opq EMDB-20153: Reconstruction of class 1 of CD4- and 17-bound B41 HIV-1 Env SOSIP incubated with LMNG and small molecule GO27 PDB-6opq: CD4- and 17-bound HIV-1 Env B41 SOSIP frozen with LMNG Method: EM (single particle) / Resolution: 3.8 Å 22048 6x5b EMDB-22048: C3 symmetric reconstruction of CD4- and 17-bound B41 HIV-1 Env SOSIP in complex with small molecule GO52 PDB-6x5b: Symmetric model of CD4- and 17-bound B41 HIV-1 Env SOSIP in complex with small molecule GO52 Method: EM (single particle) / Resolution: 3.6 Å 22049 6x5c EMDB-22049: Asymmetric reconstruction of CD4- and 17b-bound B41 HIV-1 Env SOSIP in complex with small molecule GO52 PDB-6x5c: Asymmetric model of CD4-bound B41 HIV-1 Env SOSIP in complex with small molecule GO52 Method: EM (single particle) / Resolution: 4.04 Å
Chemicals	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine ChemComp-N07: [3'-(5-methyl-1,3,4-oxadiazol-2-yl)[1,1'-biphenyl]-3-yl](piperidin-1-yl)methanone ChemComp-LMT: DODECYL-BETA-D-MALTOSIDE / detergentYM ChemComp-UOV*: N-(4'-methyl[1,1'-biphenyl]-4-yl)-1-oxa-7-azaspiro[3.5]nonane-7-carboxamide
Source	human immunodeficiency virus 1 homo sapiens (human)
Keywords	VIRAL PROTEIN/Immune System / HIV-1 / Env / CD4 / receptor-bound state / small molecule / fusion inhibitor / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex / detergent / DDM