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- PDB-7jgb: Cryo-EM structure of bedaquiline-free Mycobacterium smegmatis ATP... -
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Basic information
Entry | Database: PDB / ID: 7jgb | |||||||||
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Title | Cryo-EM structure of bedaquiline-free Mycobacterium smegmatis ATP synthase FO region | |||||||||
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![]() | HYDROLASE / Bedaquiline / Sirturo / TMC207 / T207910 / ATP synthase / mycobacteria / tuberculosis | |||||||||
Function / homology | ![]() proton motive force-driven plasma membrane ATP synthesis / photosynthetic electron transport in photosystem I / proton-transporting ATP synthase complex, coupling factor F(o) / photosynthetic electron transport in photosystem II / proton-transporting ATP synthase complex, catalytic core F(1) / proton-transporting ATPase activity, rotational mechanism / proton-transporting ATP synthase activity, rotational mechanism / membrane => GO:0016020 / hydrolase activity / lipid binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
![]() | Guo, H. / Courbon, G.M. / Rubinstein, J.L. | |||||||||
Funding support | ![]()
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![]() | ![]() 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: ![]() Title: Structure of mycobacterial ATP synthase with the TB drug bedaquiline Authors: Guo, H. / Courbon, G.M. / Bueler, S.A. / Mai, J. / Liu, J. / Rubinstein, J.L. | |||||||||
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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PDBx/mmCIF format | ![]() | 217.2 KB | Display | ![]() |
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PDB format | ![]() | 164.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 22320MC ![]() 7jg5C ![]() 7jg6C ![]() 7jg7C ![]() 7jg8C ![]() 7jg9C ![]() 7jgaC ![]() 7jgcC 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
#1: Protein | Mass: 27568.482 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#2: Protein | Mass: 17636.701 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#3: Protein | Mass: 47504.723 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#4: Protein | Mass: 8597.982 Da / Num. of mol.: 9 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: FO region of ATP synthase from Mycobacterium smegmatis Type: COMPLEX / Entity ID: all / Source: NATURAL |
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Molecular weight | Value: 0.11 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 6 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER/RHODIUM / Grid type: Homemade |
Vitrification | Instrument: FEI VITROBOT MARK III / Cryogen name: ETHANE-PROPANE / Humidity: 100 % / Chamber temperature: 277 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 / Nominal magnification: 75000 X / Calibrated defocus min: 800 nm / Calibrated defocus max: 2300 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm / Alignment procedure: ZEMLIN TABLEAU |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 45 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) / Num. of real images: 7691 |
Image scans | Width: 4096 / Height: 4096 |
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Processing
Software | Name: PHENIX / Version: 1.17.1_3660: / Classification: refinement | ||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1435679 | ||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 319756 / Algorithm: BACK PROJECTION / Num. of class averages: 3 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: RECIPROCAL | ||||||||||||||||||||||||||||||||
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