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- EMDB-0337: MicroED Structure of the CTD-SP1 fragment of HIV-1 Gag with bound... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-0337 | ||||||||||||
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Title | MicroED Structure of the CTD-SP1 fragment of HIV-1 Gag with bound maturation inhibitor Bevirimat. | ||||||||||||
![]() | MicroED map of the CTD-SP1 fragment of HIV-1 Gag with bound maturation inhibitor Bevirimat. | ||||||||||||
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![]() | Bevirimat / HIV-1 Gag / ![]() ![]() | ||||||||||||
Function / homology | ![]() host cellular component / Synthesis And Processing Of GAG, GAGPOL Polyproteins / host cell nuclear membrane / Integration of viral DNA into host genomic DNA / Autointegration results in viral DNA circles / Minus-strand DNA synthesis / Plus-strand DNA synthesis / 2-LTR circle formation / Uncoating of the HIV Virion / viral budding via host ESCRT complex ...host cellular component / Synthesis And Processing Of GAG, GAGPOL Polyproteins / host cell nuclear membrane / Integration of viral DNA into host genomic DNA / Autointegration results in viral DNA circles / Minus-strand DNA synthesis / Plus-strand DNA synthesis / 2-LTR circle formation / Uncoating of the HIV Virion / viral budding via host ESCRT complex / Vpr-mediated nuclear import of PICs / Early Phase of HIV Life Cycle / Integration of provirus / APOBEC3G mediated resistance to HIV-1 infection / Binding and entry of HIV virion / Membrane binding and targetting of GAG proteins / viral process / Assembly Of The HIV Virion / Budding and maturation of HIV virion / host multivesicular body / ![]() ![]() ![]() Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||
Method | ![]() ![]() | ||||||||||||
![]() | Purdy MD / Shi D | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: MicroED structures of HIV-1 Gag CTD-SP1 reveal binding interactions with the maturation inhibitor bevirimat. Authors: Michael D Purdy / Dan Shi / Jakub Chrustowicz / Johan Hattne / Tamir Gonen / Mark Yeager / ![]() Abstract: HIV-1 protease (PR) cleavage of the Gag polyprotein triggers the assembly of mature, infectious particles. Final cleavage of Gag occurs at the junction helix between the capsid protein CA and the SP1 ...HIV-1 protease (PR) cleavage of the Gag polyprotein triggers the assembly of mature, infectious particles. Final cleavage of Gag occurs at the junction helix between the capsid protein CA and the SP1 spacer peptide. Here we used MicroED to delineate the binding interactions of the maturation inhibitor bevirimat (BVM) using very thin frozen-hydrated, 3D microcrystals of a CTD-SP1 Gag construct with and without bound BVM. The 2.9-Å MicroED structure revealed that a single BVM molecule stabilizes the six-helix bundle via both electrostatic interactions with the dimethylsuccinyl moiety and hydrophobic interactions with the pentacyclic triterpenoid ring. These results provide insight into the mechanism of action of BVM and related maturation inhibitors that will inform further drug discovery efforts. This study also demonstrates the capabilities of MicroED for structure-based drug design. | ||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 374.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.2 KB 14.2 KB | Display Display | ![]() |
Images | ![]() | 116.8 KB | ||
Filedesc metadata | ![]() | 6.2 KB | ||
Filedesc structureFactors | ![]() | 662.8 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6n3uMC ![]() 0335C ![]() 6n3jC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | MicroED map of the CTD-SP1 fragment of HIV-1 Gag with bound maturation inhibitor Bevirimat. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.1903 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : CTD-SP1 fragment of HIV-1 Gag with bound maturation inhibitor Bev...
Entire | Name: CTD-SP1 fragment of HIV-1 Gag with bound maturation inhibitor Bevirimat |
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Components |
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-Supramolecule #1: CTD-SP1 fragment of HIV-1 Gag with bound maturation inhibitor Bev...
Supramolecule | Name: CTD-SP1 fragment of HIV-1 Gag with bound maturation inhibitor Bevirimat type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 12.17387 KDa |
-Macromolecule #1: CTD-SP1 fragment of HIV-1 Gag
Macromolecule | Name: CTD-SP1 fragment of HIV-1 Gag / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 12.192895 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: HMHHHHHHGG SPTSILDIRQ GPKEPFRDYV DRFYKTLRAE QASQEVKNWM TETLLVQNAN PDCKTILKAL GPGATLEEMM TACQGVGGP GHKARVLAEA MSQVTNTATI M UniProtKB: ![]() |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | 3D array |
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Sample preparation
Concentration | 0.4 mg/mL | |||||||||
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Buffer | pH: 7 Component:
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Grid | Model: Quantifoil R2/4 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY ARRAY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 30 sec. / Details: 30 seconds each side | |||||||||
Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV | |||||||||
Details | 10 microliters of 0.8 mg/ml protein was mixed with 10 microliters of a solution of 0.64 mM Bevirimat in DMSO/water. |
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Electron microscopy
Microscope | FEI TECNAI F20 |
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Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: DIFFRACTION![]() |
Sample stage | Specimen holder model: GATAN 626 SINGLE TILT LIQUID NITROGEN CRYO TRANSFER HOLDER Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: TVIPS TEMCAM-F416 (4k x 4k) / Number grids imaged: 5 / Average exposure time: 5.0 sec. / Average electron dose: 0.05 e/Å2 Details: Data from 5 crystals was merged for structure determination. |
Experimental equipment | ![]() Model: Tecnai F20 / Image courtesy: FEI Company |
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Image processing
Crystallography statistics | Number intensities measured: 98015 / Number structure factors: 13021 / Fourier space coverage: 83.4 / R sym: 0.544 / R merge: 0.509 / Overall phase error: 0 / Overall phase residual: 1 / Phase error rejection criteria: 0 / High resolution: 2.9 Å Shell:
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Molecular replacement | Software - Name: PHENIX (ver. dev-2747) | |||||||||||||||||||||
Final reconstruction | Resolution method: DIFFRACTION PATTERN/LAYERLINES | |||||||||||||||||||||
Merging software list | Software - Name: AIMLESS |