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Yorodumi- EMDB-21895: Monomer yeast ATP synthase (F1Fo) reconstituted in nanodisc with ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-21895 | |||||||||
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Title | Monomer yeast ATP synthase (F1Fo) reconstituted in nanodisc with inhibitor of bedaquiline bound | |||||||||
Map data | Monomer yeast ATP synthase (F1Fo) reconstituted in nanodisc with inhibitor of bedaquiline bound | |||||||||
Sample |
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Biological species | Saccharomyces cerevisiae (brewer's yeast) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Luo M / Liao MF / Mueller DM | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Commun Biol / Year: 2020 Title: Bedaquiline inhibits the yeast and human mitochondrial ATP synthases. Authors: Min Luo / Wenchang Zhou / Hiral Patel / Anurag P Srivastava / Jindrich Symersky / Michał M Bonar / José D Faraldo-Gómez / Maofu Liao / David M Mueller / Abstract: Bedaquiline (BDQ, Sirturo) has been approved to treat multidrug resistant forms of Mycobacterium tuberculosis. Prior studies suggested that BDQ was a selective inhibitor of the ATP synthase from M. ...Bedaquiline (BDQ, Sirturo) has been approved to treat multidrug resistant forms of Mycobacterium tuberculosis. Prior studies suggested that BDQ was a selective inhibitor of the ATP synthase from M. tuberculosis. However, Sirturo treatment leads to an increased risk of cardiac arrhythmias and death, raising the concern that this adverse effect results from inhibition at a secondary site. Here we show that BDQ is a potent inhibitor of the yeast and human mitochondrial ATP synthases. Single-particle cryo-EM reveals that the site of BDQ inhibition partially overlaps with that of the inhibitor oligomycin. Molecular dynamics simulations indicate that the binding mode of BDQ to this site is similar to that previously seen for a mycobacterial enzyme, explaining the observed lack of selectivity. We propose that derivatives of BDQ ought to be made to increase its specificity toward the mycobacterial enzyme and thereby reduce the side effects for patients that are treated with Sirturo. | |||||||||
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_21895.map.gz | 112.6 MB | EMDB map data format | |
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Header (meta data) | emd-21895-v30.xml emd-21895.xml | 12.7 KB 12.7 KB | Display Display | EMDB header |
Images | emd_21895.png | 64.9 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-21895 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-21895 | HTTPS FTP |
-Validation report
Summary document | emd_21895_validation.pdf.gz | 78.4 KB | Display | EMDB validaton report |
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Full document | emd_21895_full_validation.pdf.gz | 77.5 KB | Display | |
Data in XML | emd_21895_validation.xml.gz | 494 B | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21895 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21895 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_21895.map.gz / Format: CCP4 / Size: 122.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Monomer yeast ATP synthase (F1Fo) reconstituted in nanodisc with inhibitor of bedaquiline bound | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.235 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Monomer yeast ATP synthase Fo reconstituted in nanodisc generated...
Entire | Name: Monomer yeast ATP synthase Fo reconstituted in nanodisc generated in the presence of Bedaquiline |
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Components |
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-Supramolecule #1: Monomer yeast ATP synthase Fo reconstituted in nanodisc generated...
Supramolecule | Name: Monomer yeast ATP synthase Fo reconstituted in nanodisc generated in the presence of Bedaquiline type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#8 |
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Source (natural) | Organism: Saccharomyces cerevisiae (brewer's yeast) / Strain: ATCC 204508 / S288c |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1.5 mg/mL |
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Buffer | pH: 8 / Details: 20 mM Tris-HCl, 150 mM NaCl, pH 8.0 |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 400 / Support film - Material: CARBON |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 91 % |
-Electron microscopy
Microscope | FEI POLARA 300 |
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Temperature | Min: 80.0 K / Max: 105.0 K |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Number real images: 9258 / Average electron dose: 8.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Calibrated defocus max: 2.8 µm / Calibrated defocus min: 0.8 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.0 mm / Nominal magnification: 31000 |
Sample stage | Specimen holder model: GATAN LIQUID NITROGEN / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Tecnai Polara / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Initial model | PDB ID: |
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Refinement | Space: REAL |