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- EMDB-34664: Cryo-EM structure of the Mycobacterium tuberculosis cytochrome bc... -
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Open data
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Basic information
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Title | Cryo-EM structure of the Mycobacterium tuberculosis cytochrome bcc:aa3 supercomplex and a novel inhibitor targeting subunit cytochrome cI | |||||||||
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![]() | Cytochrome bcc:aa3 oxidase / Mycobacterium tuberculosis / OXIDOREDUCTASE | |||||||||
Function / homology | ![]() oxidoreduction-driven active transmembrane transporter activity / aerobic electron transport chain / cytochrome-c oxidase / oxidative phosphorylation / quinol-cytochrome-c reductase / oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen / ubiquinol-cytochrome-c reductase activity / cytochrome-c oxidase activity / electron transport coupled proton transport / : ...oxidoreduction-driven active transmembrane transporter activity / aerobic electron transport chain / cytochrome-c oxidase / oxidative phosphorylation / quinol-cytochrome-c reductase / oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen / ubiquinol-cytochrome-c reductase activity / cytochrome-c oxidase activity / electron transport coupled proton transport / : / monooxygenase activity / aerobic respiration / respiratory electron transport chain / 2 iron, 2 sulfur cluster binding / electron transfer activity / iron ion binding / heme binding / membrane / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | electron tomography / cryo EM | |||||||||
![]() | Mathiyazakan V / Gruber G | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-Electron Microscopy Structure of the s Cytochrome : Supercomplex and a Novel Inhibitor Targeting Subunit Cytochrome I. Authors: Vikneswaran Mathiyazakan / Chui-Fann Wong / Amaravadhi Harikishore / Kevin Pethe / Gerhard Grüber / ![]() Abstract: The mycobacterial cytochrome complex deserves the name "supercomplex" since it combines three cytochrome oxidases-cytochrome , cytochrome , and cytochrome -into one supramolecular machine and ...The mycobacterial cytochrome complex deserves the name "supercomplex" since it combines three cytochrome oxidases-cytochrome , cytochrome , and cytochrome -into one supramolecular machine and performs electron transfer for the reduction of oxygen to water and proton transport to generate the proton motive force for ATP synthesis. Thus, the complex represents a valid drug target for Mycobacterium tuberculosis infections. The production and purification of an entire M. tuberculosis cytochrome are fundamental for biochemical and structural characterization of this supercomplex, paving the way for new inhibitor targets and molecules. Here, we produced and purified the entire and active M. tuberculosis cyt- oxidase, as demonstrated by the different heme spectra and an oxygen consumption assay. The resolved M. tuberculosis cyt- cryo-electron microscopy structure reveals a dimer with its functional domains involved in electron, proton, oxygen transfer, and oxygen reduction. The structure shows the two cytochrome III head domains of the dimer, the counterpart of the soluble mitochondrial cytochrome , in a so-called "closed state," in which electrons are translocated from the to the domain. The structural and mechanistic insights provided the basis for a virtual screening campaign that identified a potent M. tuberculosis cyt- inhibitor, cyt1. cyt1 targets the mycobacterium-specific α3-helix of cytochrome I and interferes with oxygen consumption by interrupting electron translocation via the III head. The successful identification of a new cyt- inhibitor demonstrates the potential of a structure-mechanism-based approach for novel compound development. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 450.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 21.7 KB 21.7 KB | Display Display | ![]() |
Images | ![]() | 84.9 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8hcrMC M: atomic model generated by this map C: citing same article ( |
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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: 1.06 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 : Cytochrome bcc:aa3 supercomplex
+Supramolecule #1: Cytochrome bcc:aa3 supercomplex
+Macromolecule #1: Cytochrome bc1 complex Rieske iron-sulfur subunit
+Macromolecule #2: Cytochrome bc1 complex cytochrome b subunit
+Macromolecule #3: Cytochrome bc1 complex cytochrome c subunit
+Macromolecule #4: CYTOCHROME AA3 SUBUNIT CtaC
+Macromolecule #5: Probable cytochrome c oxidase subunit 1
+Macromolecule #6: Probable cytochrome c oxidase subunit 3
+Macromolecule #7: Cytochrome c oxidase polypeptide 4
+Macromolecule #8: CYTOCHROME AA3 SUBUNIT CtaJ
+Macromolecule #9: DUF5130 domain-containing protein
+Macromolecule #10: FE2/S2 (INORGANIC) CLUSTER
+Macromolecule #11: PROTOPORPHYRIN IX CONTAINING FE
+Macromolecule #12: HEME C
+Macromolecule #13: HEME-A
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | electron tomography |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
Sectioning | Other: NO SECTIONING |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Number images used: 100 |
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