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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-24457 | ||||||||||||
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Title | Mycobacterial CIII2CIV2 supercomplex, Telacebec (Q203) bound | ||||||||||||
![]() | Mycobacterium CIII2CIV2 supercomplex, telacebec bound. | ||||||||||||
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Function / homology | ![]() aerobic electron transport chain / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | ![]() ![]() | ||||||||||||
![]() | Di Trani JM / Yanofsky DJ / Rubinstein JL | ||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: Structure of mycobacterial CIIICIV respiratory supercomplex bound to the tuberculosis drug candidate telacebec (Q203). Authors: David J Yanofsky / Justin M Di Trani / Sylwia Król / Rana Abdelaziz / Stephanie A Bueler / Peter Imming / Peter Brzezinski / John L Rubinstein / ![]() ![]() ![]() Abstract: The imidazopyridine telacebec, also known as Q203, is one of only a few new classes of compounds in more than 50 years with demonstrated antituberculosis activity in humans. Telacebec inhibits the ...The imidazopyridine telacebec, also known as Q203, is one of only a few new classes of compounds in more than 50 years with demonstrated antituberculosis activity in humans. Telacebec inhibits the mycobacterial respiratory supercomplex composed of complexes III and IV (CIIICIV). In mycobacterial electron transport chains, CIIICIV replaces canonical CIII and CIV, transferring electrons from the intermediate carrier menaquinol to the final acceptor, molecular oxygen, while simultaneously transferring protons across the inner membrane to power ATP synthesis. We show that telacebec inhibits the menaquinol:oxygen oxidoreductase activity of purified CIIICIV at concentrations similar to those needed to inhibit electron transfer in mycobacterial membranes and growth in culture. We then used electron cryomicroscopy (cryoEM) to determine structures of CIIICIV both in the presence and absence of telacebec. The structures suggest that telacebec prevents menaquinol oxidation by blocking two different menaquinol binding modes to prevent CIIICIV activity. | ||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 102.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 27 KB 27 KB | Display Display | ![]() |
Images | ![]() | 77.4 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7rh7MC ![]() 7rh5C ![]() 7rh6C C: citing same article ( M: atomic model generated by this map |
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Similar structure data |
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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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Annotation | Mycobacterium CIII2CIV2 supercomplex, telacebec bound. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
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Sample components
+Entire : Respiratory Complex CIII2CIV2SOD2 from Mycobacterium smegmatis
+Supramolecule #1: Respiratory Complex CIII2CIV2SOD2 from Mycobacterium smegmatis
+Macromolecule #1: LpqE protein
+Macromolecule #2: Cytochrome aa3 subunit 2
+Macromolecule #3: Cytochrome c oxidase subunit 1
+Macromolecule #4: Cytochrome aa3 subunit 3
+Macromolecule #5: Cytochrome c oxidase polypeptide 4
+Macromolecule #6: Cytochrome c oxidase subunit CtaJ
+Macromolecule #7: Uncharacterized protein MSMEG_4692/MSMEI_4575
+Macromolecule #8: Conserved transmembrane protein
+Macromolecule #9: Superoxide dismutase [Cu-Zn]
+Macromolecule #10: Cytochrome bc1 complex cytochrome c subunit
+Macromolecule #11: Cytochrome bc1 complex cytochrome b subunit
+Macromolecule #12: Cytochrome bc1 complex Rieske iron-sulfur subunit
+Macromolecule #13: (2S)-1-(hexadecanoyloxy)propan-2-yl (10S)-10-methyloctadecanoate
+Macromolecule #14: PALMITIC ACID
+Macromolecule #15: COPPER (II) ION
+Macromolecule #16: HEME-A
+Macromolecule #17: CARDIOLIPIN
+Macromolecule #18: (2R)-3-(((2-aminoethoxy)(hydroxy)phosphoryl)oxy)-2-(palmitoyloxy)...
+Macromolecule #19: MENAQUINONE-9
+Macromolecule #20: HEME C
+Macromolecule #21: (2R)-2-(hexadecanoyloxy)-3-{[(S)-hydroxy{[(1R,2R,3R,4R,5R,6S)-2,3...
+Macromolecule #22: PROTOPORPHYRIN IX CONTAINING FE
+Macromolecule #23: 6-chloranyl-2-ethyl-N-[[4-[4-[4-(trifluoromethyloxy)phenyl]piperi...
+Macromolecule #24: FE2/S2 (INORGANIC) CLUSTER
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE-PROPANE |
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Electron microscopy
Microscope | TFS KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 43.5 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
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Final angle assignment | Type: ANGULAR RECONSTITUTION |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 70818 |
-Atomic model buiding 1
Refinement | Space: REAL |
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Output model | ![]() PDB-7rh7: |