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- EMDB-35911: Cryo-EM structure of Mycobacterium tuberculosis ATP synthase in t... -
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Basic information
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Title | Cryo-EM structure of Mycobacterium tuberculosis ATP synthase in the apo-form | ||||||||||||
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![]() | ATP synthase / Mycobacterium tuberculosis / cryo-EM / MEMBRANE PROTEIN | ||||||||||||
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) / proton motive force-driven ATP synthesis / 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 / peptidoglycan-based cell wall ...proton motive force-driven plasma membrane ATP synthesis / photosynthetic electron transport in photosystem I / proton-transporting ATP synthase complex, coupling factor F(o) / proton motive force-driven ATP synthesis / 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 / peptidoglycan-based cell wall / ADP binding / hydrolase activity / lipid binding / ATP hydrolysis activity / extracellular region / ATP binding / plasma membrane / cytosol Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | ||||||||||||
![]() | Zhang Y / Lai Y / Liu F / Rao Z / Gong H | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Inhibition of M. tuberculosis and human ATP synthase by BDQ and TBAJ-587. Authors: Yuying Zhang / Yuezheng Lai / Shan Zhou / Ting Ran / Yue Zhang / Ziqing Zhao / Ziyan Feng / Long Yu / Jinxu Xu / Kun Shi / Jianyun Wang / Yu Pang / Liang Li / Hongming Chen / Luke W Guddat / ...Authors: Yuying Zhang / Yuezheng Lai / Shan Zhou / Ting Ran / Yue Zhang / Ziqing Zhao / Ziyan Feng / Long Yu / Jinxu Xu / Kun Shi / Jianyun Wang / Yu Pang / Liang Li / Hongming Chen / Luke W Guddat / Yan Gao / Fengjiang Liu / Zihe Rao / Hongri Gong / ![]() ![]() Abstract: Bedaquiline (BDQ), a first-in-class diarylquinoline anti-tuberculosis drug, and its analogue, TBAJ-587, prevent the growth and proliferation of Mycobacterium tuberculosis by inhibiting ATP synthase. ...Bedaquiline (BDQ), a first-in-class diarylquinoline anti-tuberculosis drug, and its analogue, TBAJ-587, prevent the growth and proliferation of Mycobacterium tuberculosis by inhibiting ATP synthase. However, BDQ also inhibits human ATP synthase. At present, how these compounds interact with either M. tuberculosis ATP synthase or human ATP synthase is unclear. Here we present cryogenic electron microscopy structures of M. tuberculosis ATP synthase with and without BDQ and TBAJ-587 bound, and human ATP synthase bound to BDQ. The two inhibitors interact with subunit a and the c-ring at the leading site, c-only sites and lagging site in M. tuberculosis ATP synthase, showing that BDQ and TBAJ-587 have similar modes of action. The quinolinyl and dimethylamino units of the compounds make extensive contacts with the protein. The structure of human ATP synthase in complex with BDQ reveals that the BDQ-binding site is similar to that observed for the leading site in M. tuberculosis ATP synthase, and that the quinolinyl unit also interacts extensively with the human enzyme. This study will improve researchers' understanding of the similarities and differences between human ATP synthase and M. tuberculosis ATP synthase in terms of the mode of BDQ binding, and will allow the rational design of novel diarylquinolines as anti-tuberculosis drugs. | ||||||||||||
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 467.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 22.1 KB 22.1 KB | Display Display | ![]() |
Images | ![]() | 41.5 KB | ||
Filedesc metadata | ![]() | 7.5 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8j0tMC ![]() 8j0sC ![]() 8j57C ![]() 8j58C ![]() 8jr0C ![]() 8jr1C ![]() 8khfC ![]() 8ki3C ![]() 37029 C: citing same article ( M: atomic model generated by this map |
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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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Voxel size | X=Y=Z: 0.73 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
+Entire : Mycobacterium tuberculosis ATP synthase
+Supramolecule #1: Mycobacterium tuberculosis ATP synthase
+Macromolecule #1: ATP synthase subunit alpha
+Macromolecule #2: ATP synthase subunit beta
+Macromolecule #3: ATP synthase gamma chain
+Macromolecule #4: ATP synthase epsilon chain
+Macromolecule #5: ATP synthase subunit c
+Macromolecule #6: ATP synthase subunit a
+Macromolecule #7: ATP synthase subunit b
+Macromolecule #8: Multifunctional fusion protein
+Macromolecule #9: ADENOSINE-5'-TRIPHOSPHATE
+Macromolecule #10: MAGNESIUM ION
+Macromolecule #11: ADENOSINE-5'-DIPHOSPHATE
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.4 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: OTHER / Details: AlphaFold |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 66593 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |