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Yorodumi- EMDB-29650: Cryo-EM structure of SQ31f-bound Mycobacterium smegmatis ATP synt... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-29650 | |||||||||
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Title | Cryo-EM structure of SQ31f-bound Mycobacterium smegmatis ATP synthase rotational state 2 | |||||||||
Map data | Cryo-EM structure of SQ31f-bound Mycobacterium smegmatis ATP synthase rotational state 2 (unsharpened) | |||||||||
Sample |
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Keywords | ATP synthase / mycobacterial / inhibitor / tuberculosis / antibiotic / HYDROLASE / TRANSLOCASE-INHIBITOR complex | |||||||||
Function / homology | Function and homology information 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) / H+-transporting two-sector ATPase / proton-transporting ATPase activity, rotational mechanism / proton-transporting ATP synthase activity, rotational mechanism / ADP binding / hydrolase activity ...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) / H+-transporting two-sector ATPase / proton-transporting ATPase activity, rotational mechanism / proton-transporting ATP synthase activity, rotational mechanism / ADP binding / hydrolase activity / lipid binding / ATP hydrolysis activity / ATP binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Mycolicibacterium smegmatis MC2 155 (bacteria) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
Authors | Courbon GM / Rubinstein JL | |||||||||
Funding support | Canada, 1 items
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Citation | Journal: EMBO J / Year: 2023 Title: Mechanism of mycobacterial ATP synthase inhibition by squaramides and second generation diarylquinolines. Authors: Gautier M Courbon / Paul R Palme / Lea Mann / Adrian Richter / Peter Imming / John L Rubinstein / Abstract: Mycobacteria, such as Mycobacterium tuberculosis, depend on the activity of adenosine triphosphate (ATP) synthase for growth. The diarylquinoline bedaquiline (BDQ), a mycobacterial ATP synthase ...Mycobacteria, such as Mycobacterium tuberculosis, depend on the activity of adenosine triphosphate (ATP) synthase for growth. The diarylquinoline bedaquiline (BDQ), a mycobacterial ATP synthase inhibitor, is an important medication for treatment of drug-resistant tuberculosis but suffers from off-target effects and is susceptible to resistance mutations. Consequently, both new and improved mycobacterial ATP synthase inhibitors are needed. We used electron cryomicroscopy and biochemical assays to study the interaction of Mycobacterium smegmatis ATP synthase with the second generation diarylquinoline TBAJ-876 and the squaramide inhibitor SQ31f. The aryl groups of TBAJ-876 improve binding compared with BDQ, while SQ31f, which blocks ATP synthesis ~10 times more potently than ATP hydrolysis, binds a previously unknown site in the enzyme's proton-conducting channel. Remarkably, BDQ, TBAJ-876, and SQ31f all induce similar conformational changes in ATP synthase, suggesting that the resulting conformation is particularly suited for drug binding. Further, high concentrations of the diarylquinolines uncouple the transmembrane proton motive force while for SQ31f they do not, which may explain why high concentrations of diarylquinolines, but not SQ31f, have been reported to kill mycobacteria. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_29650.map.gz | 62.8 MB | EMDB map data format | |
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Header (meta data) | emd-29650-v30.xml emd-29650.xml | 26.9 KB 26.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_29650_fsc.xml | 10.6 KB | Display | FSC data file |
Images | emd_29650.png | 66.1 KB | ||
Filedesc metadata | emd-29650.cif.gz | 7.3 KB | ||
Others | emd_29650_additional_1.map.gz emd_29650_half_map_1.map.gz emd_29650_half_map_2.map.gz | 57.2 MB 116.2 MB 116.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-29650 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-29650 | HTTPS FTP |
-Validation report
Summary document | emd_29650_validation.pdf.gz | 959.4 KB | Display | EMDB validaton report |
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Full document | emd_29650_full_validation.pdf.gz | 958.9 KB | Display | |
Data in XML | emd_29650_validation.xml.gz | 19 KB | Display | |
Data in CIF | emd_29650_validation.cif.gz | 24.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29650 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29650 | HTTPS FTP |
-Related structure data
Related structure data | 8g09MC 8g07C 8g08C 8g0aC 8g0bC 8g0cC 8g0dC 8g0eC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_29650.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Cryo-EM structure of SQ31f-bound Mycobacterium smegmatis ATP synthase rotational state 2 (unsharpened) | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.03 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Cryo-EM structure of SQ31f-bound Mycobacterium smegmatis ATP synthase...
File | emd_29650_additional_1.map | ||||||||||||
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Annotation | Cryo-EM structure of SQ31f-bound Mycobacterium smegmatis ATP synthase rotational state 2 (locally sharpened) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Cryo-EM structure of SQ31f-bound Mycobacterium smegmatis ATP synthase...
File | emd_29650_half_map_1.map | ||||||||||||
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Annotation | Cryo-EM structure of SQ31f-bound Mycobacterium smegmatis ATP synthase rotational state 2 (Half A) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Cryo-EM structure of SQ31f-bound Mycobacterium smegmatis ATP synthase...
File | emd_29650_half_map_2.map | ||||||||||||
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Annotation | Cryo-EM structure of SQ31f-bound Mycobacterium smegmatis ATP synthase rotational state 2 (Half B) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : SQ31f-bound Mycobacterium smegmatis ATP synthase rotational state 2
+Supramolecule #1: SQ31f-bound Mycobacterium smegmatis ATP synthase rotational state 2
+Macromolecule #1: ATP synthase subunit c
+Macromolecule #2: ATP synthase subunit alpha
+Macromolecule #3: ATP synthase subunit beta
+Macromolecule #4: ATP synthase gamma chain
+Macromolecule #5: ATP synthase epsilon chain
+Macromolecule #6: ATP synthase subunit a
+Macromolecule #7: ATP synthase subunit b
+Macromolecule #8: ATP synthase subunit b-delta
+Macromolecule #9: ADENOSINE-5'-TRIPHOSPHATE
+Macromolecule #10: MAGNESIUM ION
+Macromolecule #11: PHOSPHATE ION
+Macromolecule #12: 3-[4-(morpholin-4-yl)phenyl]-4-{[(pyridin-2-yl)methyl]amino}cyclo...
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 54.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.9 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |