+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-24455 | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Mycobacterial CIII2CIV2 supercomplex, Inhibitor free | ||||||||||||
Map data | Mycobacterium CIII2CIV2 supercomplex, inhibitor free. | ||||||||||||
Sample |
| ||||||||||||
Function / homology | Function and homology information aerobic electron transport chain / cytochrome-c oxidase / quinol-cytochrome-c reductase / ubiquinol-cytochrome-c reductase activity / cytochrome-c oxidase activity / superoxide dismutase / superoxide dismutase activity / : / respiratory electron transport chain / electron transport chain ...aerobic electron transport chain / cytochrome-c oxidase / quinol-cytochrome-c reductase / ubiquinol-cytochrome-c reductase activity / cytochrome-c oxidase activity / superoxide dismutase / superoxide dismutase activity / : / respiratory electron transport chain / electron transport chain / 2 iron, 2 sulfur cluster binding / iron ion binding / copper ion binding / heme binding / membrane / metal ion binding / plasma membrane Similarity search - Function | ||||||||||||
Biological species | Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (bacteria) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | ||||||||||||
Authors | Di Trani JM / Yanofsky DJ / Rubinstein JL | ||||||||||||
Funding support | Canada, Sweden, 3 items
| ||||||||||||
Citation | Journal: Elife / Year: 2021 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 |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_24455.map.gz | 100.9 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-24455-v30.xml emd-24455.xml | 26.7 KB 26.7 KB | Display Display | EMDB header |
Images | emd_24455.png | 113 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-24455 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-24455 | HTTPS FTP |
-Validation report
Summary document | emd_24455_validation.pdf.gz | 485.9 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_24455_full_validation.pdf.gz | 485.4 KB | Display | |
Data in XML | emd_24455_validation.xml.gz | 6.8 KB | Display | |
Data in CIF | emd_24455_validation.cif.gz | 7.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24455 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24455 | HTTPS FTP |
-Related structure data
Related structure data | 7rh5MC 7rh6C 7rh7C C: citing same article (ref.) M: atomic model generated by this map |
---|---|
Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_24455.map.gz / Format: CCP4 / Size: 137.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Mycobacterium CIII2CIV2 supercomplex, inhibitor free. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.03 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Sample components
+Entire : Respiratory supercomplex CIII2CIV2SOD2 from Mycobacterium smegmatis
+Supramolecule #1: Respiratory supercomplex CIII2CIV2SOD2 from Mycobacterium smegmatis
+Macromolecule #1: Cytochrome c oxidase subunit 1
+Macromolecule #2: Cytochrome bc1 complex cytochrome b subunit
+Macromolecule #3: Superoxide dismutase [Cu-Zn]
+Macromolecule #4: Cytochrome aa3 subunit 2
+Macromolecule #5: Cytochrome aa3 subunit 3
+Macromolecule #6: Cytochrome c oxidase polypeptide 4
+Macromolecule #7: Cytochrome c oxidase subunit CtaJ
+Macromolecule #8: Uncharacterized protein MSMEG_4692/MSMEI_4575
+Macromolecule #9: Putative conserved transmembrane protein
+Macromolecule #10: Cytochrome bc1 complex cytochrome c subunit
+Macromolecule #11: LpqE protein
+Macromolecule #12: Cytochrome bc1 complex Rieske iron-sulfur subunit
+Macromolecule #13: COPPER (II) ION
+Macromolecule #14: HEME-A
+Macromolecule #15: CARDIOLIPIN
+Macromolecule #16: PROTOPORPHYRIN IX CONTAINING FE
+Macromolecule #17: MENAQUINONE-9
+Macromolecule #18: (2R)-3-(((2-aminoethoxy)(hydroxy)phosphoryl)oxy)-2-(palmitoyloxy)...
+Macromolecule #19: PALMITIC ACID
+Macromolecule #20: (2S)-1-(hexadecanoyloxy)propan-2-yl (10S)-10-methyloctadecanoate
+Macromolecule #21: HEME C
+Macromolecule #22: (2R)-2-(hexadecanoyloxy)-3-{[(S)-hydroxy{[(1R,2R,3R,4R,5R,6S)-2,3...
+Macromolecule #23: FE2/S2 (INORGANIC) CLUSTER
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
---|---|
Vitrification | Cryogen name: ETHANE-PROPANE |
-Electron microscopy
Microscope | TFS KRIOS |
---|---|
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 43.5 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 150885 |
---|---|
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: ANGULAR RECONSTITUTION |
-Atomic model buiding 1
Refinement | Space: REAL |
---|---|
Output model | PDB-7rh5: |