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Yorodumi- PDB-7rh6: Mycobacterial CIII2CIV2 supercomplex, inhibitor free, -Lpqe cyt c... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7rh6 | ||||||||||||
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Title | Mycobacterial CIII2CIV2 supercomplex, inhibitor free, -Lpqe cyt cc open | ||||||||||||
Components |
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Keywords | MEMBRANE PROTEIN / Electron transport chain / CIII2CIV2 supercomplex | ||||||||||||
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 (bacteria) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||||||||
Authors | Di Trani, J.M. / Yanofsky, D.J. / Rubinstein, J.L. | ||||||||||||
Funding support | Canada, Sweden, 3items
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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 |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7rh6.cif.gz | 1.8 MB | Display | PDBx/mmCIF format |
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PDB format | pdb7rh6.ent.gz | 1.6 MB | Display | PDB format |
PDBx/mmJSON format | 7rh6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7rh6_validation.pdf.gz | 2.9 MB | Display | wwPDB validaton report |
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Full document | 7rh6_full_validation.pdf.gz | 3.2 MB | Display | |
Data in XML | 7rh6_validation.xml.gz | 198.1 KB | Display | |
Data in CIF | 7rh6_validation.cif.gz | 262.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rh/7rh6 ftp://data.pdbj.org/pub/pdb/validation_reports/rh/7rh6 | HTTPS FTP |
-Related structure data
Related structure data | 24456MC 7rh5C 7rh7C C: citing same article (ref.) M: map data used to model this data |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Cytochrome bc1 complex cytochrome ... , 2 types, 4 molecules OIEF
#1: Protein | Mass: 23183.990 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (bacteria) Strain: ATCC 700084 / mc(2)155 / References: UniProt: I7FPH1, quinol-cytochrome-c reductase #5: Protein | Mass: 59110.758 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (bacteria) Strain: ATCC 700084 / mc(2)155 / References: UniProt: I7FGS8, quinol-cytochrome-c reductase |
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-Cytochrome c oxidase subunit ... , 2 types, 4 molecules RLUa
#2: Protein | Mass: 61733.234 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (bacteria) Strain: ATCC 700084 / mc(2)155 / References: cytochrome-c oxidase #10: Protein | Mass: 8365.549 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (bacteria) Strain: ATCC 700084 / mc(2)155 / References: UniProt: I7FQK8 |
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-Protein , 6 types, 11 molecules MYJPDGTZVbc
#3: Protein | Mass: 42210.484 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (bacteria) Strain: ATCC 700084 / mc(2)155 / References: UniProt: I7GD61 #6: Protein | Mass: 11329.909 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (bacteria) Strain: ATCC 700084 / mc(2)155 #7: Protein | Mass: 21221.863 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (bacteria) Strain: ATCC 700084 / mc(2)155 / References: UniProt: I7G2H6, superoxide dismutase #9: Protein | Mass: 15177.424 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (bacteria) Strain: ATCC 700084 / mc(2)155 / References: UniProt: I7FPH7, cytochrome-c oxidase #11: Protein | Mass: 14808.747 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (bacteria) Strain: ATCC 700084 / mc(2)155 / References: UniProt: A0R1B5 #12: Protein | | Mass: 16412.873 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (bacteria) Strain: ATCC 700084 / mc(2)155 / References: UniProt: I7GFE1 |
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-Cytochrome aa3 subunit ... , 2 types, 4 molecules SXQK
#4: Protein | Mass: 22196.883 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (bacteria) Strain: ATCC 700084 / mc(2)155 / References: UniProt: A0R049 #8: Protein | Mass: 35201.008 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (bacteria) Strain: ATCC 700084 / mc(2)155 / References: UniProt: I7GD63, cytochrome-c oxidase |
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-Non-polymers , 11 types, 60 molecules
#13: Chemical | ChemComp-HEC / #14: Chemical | ChemComp-9YF / ( #15: Chemical | ChemComp-MQ9 / #16: Chemical | ChemComp-CU / #17: Chemical | ChemComp-HEA / #18: Chemical | ChemComp-CDL / #19: Chemical | #20: Chemical | ChemComp-9Y0 / ( #21: Chemical | ChemComp-HEM / #22: Chemical | #23: Chemical | |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Respiratory Complex CIII2CIV2SOD2 from Mycobacterium smegmatis Type: COMPLEX / Entity ID: #1, #8-#12 / Source: NATURAL |
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Source (natural) | Organism: Mycolicibacterium smegmatis MC2 155 (bacteria) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE-PROPANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 43.5 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 150885 / Symmetry type: POINT |
Atomic model building | Space: REAL |