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Open data
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Basic information
Entry | Database: PDB / ID: 6opq | ||||||||||||
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Title | CD4- and 17-bound HIV-1 Env B41 SOSIP frozen with LMNG | ||||||||||||
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Function / homology | ![]() helper T cell enhancement of adaptive immune response / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||||||||
Method | ![]() ![]() ![]() | ||||||||||||
![]() | Ozorowski, G. / Torres, J.L. / Ward, A.B. | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: A Strain-Specific Inhibitor of Receptor-Bound HIV-1 Targets a Pocket near the Fusion Peptide. Authors: Gabriel Ozorowski / Jonathan L Torres / Diogo Santos-Martins / Stefano Forli / Andrew B Ward / ![]() 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. #1: ![]() Title: A strain-specific inhibitor of receptor-bound HIV-1 targets a pocket near the fusion peptide and offers a template for drug design Authors: Ozorowski, G. / Torres, J.L. / Santos-Martins, D. / Forli, S. / Ward, A.B. | ||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 543.9 KB | Display | ![]() |
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PDB format | ![]() | 445.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 20153MC ![]() 6opnC ![]() 6opoC ![]() 6oppC ![]() 6x5bC ![]() 6x5cC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Envelope glycoprotein ... , 2 types, 6 molecules ADEBFG
#1: Protein | Mass: 58872.902 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() #3: Protein | Mass: 17357.824 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() |
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-Protein , 1 types, 3 molecules CIJ
#4: Protein | Mass: 23039.172 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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-Antibody , 2 types, 6 molecules LNOHKM
#2: Antibody | Mass: 23425.869 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #5: Antibody | Mass: 24484.455 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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-Sugars , 3 types, 36 molecules ![](data/chem/img/NAG.gif)
#6: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose ![]() Source method: isolated from a genetically manipulated source #7: Polysaccharide | ![]() Source method: isolated from a genetically manipulated source #8: Sugar | ChemComp-NAG / ![]() |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
Component | Name: Class 1 of CD4- and 17b-bound HIV-1 Env B41 SOSIP incubated with LMNG and small molecule GO27 Type: COMPLEX / Entity ID: #1-#5 / Source: MULTIPLE SOURCES | ||||||||||||||||||||
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Molecular weight |
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Source (natural) | Organism: ![]() ![]() ![]() | ||||||||||||||||||||
Source (recombinant) | Organism: ![]() ![]() | ||||||||||||||||||||
Buffer solution | pH: 7.4 / Details: Detergent (LMNG) added shortly (<5 minutes) prior to grid freezing using an 8X concentrated stock. | ||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() Details: Complex of CD4- and 17b-bound B41 SOSIP was SEC purified and GO27 was diluted 1:100 into the complex and incubated for 15 minutes prior to grid freezing. | ||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 400 divisions/in. / Grid type: C-flat-2/2 | ||||||||||||||||||||
Vitrification![]() | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 283 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() ![]() |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 12.5 sec. / Electron dose: 51 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of real images: 5296 |
Image scans | Sampling size: 5 µm / Movie frames/image: 50 |
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Processing
EM software |
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CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry![]() ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 100406 Details: FSC resolution estimated using CryoSPARC 2 and Relion 3.0 Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 5VN3 |