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Yorodumi- EMDB-22319: Cryo-EM structure of bedaquiline-washed Mycobacterium smegmatis A... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-22319 | |||||||||
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Title | Cryo-EM structure of bedaquiline-washed Mycobacterium smegmatis ATP synthase rotational state 3 | |||||||||
Map data | Locally sharpened map. | |||||||||
Sample |
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Biological species | Mycolicibacterium smegmatis (bacteria) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Guo H / Courbon GM / Rubinstein JL | |||||||||
Funding support | Canada, 2 items
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Citation | Journal: Nature / Year: 2021 Title: Structure of mycobacterial ATP synthase bound to the tuberculosis drug bedaquiline. Authors: Hui Guo / Gautier M Courbon / Stephanie A Bueler / Juntao Mai / Jun Liu / John L Rubinstein / Abstract: Tuberculosis-the world's leading cause of death by infectious disease-is increasingly resistant to current first-line antibiotics. The bacterium Mycobacterium tuberculosis (which causes tuberculosis) ...Tuberculosis-the world's leading cause of death by infectious disease-is increasingly resistant to current first-line antibiotics. The bacterium Mycobacterium tuberculosis (which causes tuberculosis) can survive low-energy conditions, allowing infections to remain dormant and decreasing their susceptibility to many antibiotics. Bedaquiline was developed in 2005 from a lead compound identified in a phenotypic screen against Mycobacterium smegmatis. This drug can sterilize even latent M. tuberculosis infections and has become a cornerstone of treatment for multidrug-resistant and extensively drug-resistant tuberculosis. Bedaquiline targets the mycobacterial ATP synthase, which is an essential enzyme in the obligate aerobic Mycobacterium genus, but how it binds the intact enzyme is unknown. Here we determined cryo-electron microscopy structures of M. smegmatis ATP synthase alone and in complex with bedaquiline. The drug-free structure suggests that hook-like extensions from the α-subunits prevent the enzyme from running in reverse, inhibiting ATP hydrolysis and preserving energy in hypoxic conditions. Bedaquiline binding induces large conformational changes in the ATP synthase, creating tight binding pockets at the interface of subunits a and c that explain the potency of this drug as an antibiotic for tuberculosis. #1: Journal: Biorxiv / Year: 2020 Title: Structure of mycobacterial ATP synthase with the TB drug bedaquiline Authors: Guo H / Courbon GM / Bueler SA / Mai J / Liu J / Rubinstein JL | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_22319.map.gz | 58 MB | EMDB map data format | |
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Header (meta data) | emd-22319-v30.xml emd-22319.xml | 21.6 KB 21.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_22319_fsc.xml | 11.4 KB | Display | FSC data file |
Images | emd_22319.png | 106.5 KB | ||
Masks | emd_22319_msk_1.map | 125 MB | Mask map | |
Others | emd_22319_additional.map.gz emd_22319_additional_1.map.gz emd_22319_half_map_1.map.gz emd_22319_half_map_2.map.gz | 62.4 MB 62.4 MB 116.2 MB 116.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-22319 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22319 | HTTPS FTP |
-Validation report
Summary document | emd_22319_validation.pdf.gz | 542.5 KB | Display | EMDB validaton report |
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Full document | emd_22319_full_validation.pdf.gz | 542.1 KB | Display | |
Data in XML | emd_22319_validation.xml.gz | 17.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22319 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22319 | HTTPS FTP |
-Related structure data
Related structure data | 7jg5C 7jg6C 7jg7C 7jg8C 7jg9C 7jgaC 7jgbC 7jgcC C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_22319.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Locally sharpened map. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.03 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_22319_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: Unsharpened map.
File | emd_22319_additional.map | ||||||||||||
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Annotation | Unsharpened map. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Unsharpened map.
File | emd_22319_additional_1.map | ||||||||||||
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Annotation | Unsharpened map. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 1.
File | emd_22319_half_map_1.map | ||||||||||||
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Annotation | Half map 1. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 2.
File | emd_22319_half_map_2.map | ||||||||||||
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Annotation | Half map 2. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : ATP synthase from Mycobacterium smegmatis
Entire | Name: ATP synthase from Mycobacterium smegmatis |
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Components |
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-Supramolecule #1: ATP synthase from Mycobacterium smegmatis
Supramolecule | Name: ATP synthase from Mycobacterium smegmatis / type: complex / ID: 1 / Parent: 0 |
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Source (natural) | Organism: Mycolicibacterium smegmatis (bacteria) |
Molecular weight | Theoretical: 550 KDa |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 6 mg/mL |
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Buffer | pH: 7.4 |
Grid | Model: Homemade / Material: COPPER/RHODIUM / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: OTHER |
Vitrification | Cryogen name: ETHANE-PROPANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK III |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Digitization - Dimensions - Width: 4096 pixel / Digitization - Dimensions - Height: 4096 pixel / Number real images: 4962 / Average electron dose: 41.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Calibrated defocus max: 4.0 µm / Calibrated defocus min: 0.5 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal magnification: 75000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: RECIPROCAL / Protocol: AB INITIO MODEL |
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