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Yorodumi- EMDB-4292: CryoEM structure of bovine cytochrome bc1 in complex with the ant... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-4292 | |||||||||
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Title | CryoEM structure of bovine cytochrome bc1 in complex with the anti-malarial inhibitor SCR0911 | |||||||||
Map data | The cryoEM map of bovine cytochrome bc1 in complex with the anti-malarial inhibitor SCR0911 | |||||||||
Sample |
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Function / homology | Function and homology information Complex III assembly / respiratory chain complex III / Respiratory electron transport / : / quinol-cytochrome-c reductase / ubiquinol-cytochrome-c reductase activity / mitochondrial electron transport, ubiquinol to cytochrome c / ubiquinone binding / Mitochondrial protein degradation / : ...Complex III assembly / respiratory chain complex III / Respiratory electron transport / : / quinol-cytochrome-c reductase / ubiquinol-cytochrome-c reductase activity / mitochondrial electron transport, ubiquinol to cytochrome c / ubiquinone binding / Mitochondrial protein degradation / : / respiratory electron transport chain / mitochondrial membrane / metalloendopeptidase activity / 2 iron, 2 sulfur cluster binding / mitochondrial inner membrane / oxidoreductase activity / heme binding / mitochondrion / proteolysis / membrane / metal ion binding Similarity search - Function | |||||||||
Biological species | Bos taurus (cattle) / Bovine (cattle) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.1 Å | |||||||||
Authors | Johnson RM / Amporndanai K / O'Neill PM / Fishwick CWG / Jamson AH / Rawson SD / Hasnain SS / Antonyuk SV / Muench SP | |||||||||
Funding support | United Kingdom, 1 items
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Citation | Journal: IUCrJ / Year: 2018 Title: X-ray and cryo-EM structures of inhibitor-bound cytochrome complexes for structure-based drug discovery. Authors: Kangsa Amporndanai / Rachel M Johnson / Paul M O'Neill / Colin W G Fishwick / Alexander H Jamson / Shaun Rawson / Stephen P Muench / S Samar Hasnain / Svetlana V Antonyuk / Abstract: Cytochrome , a dimeric multi-subunit electron-transport protein embedded in the inner mitochondrial membrane, is a major drug target for the treatment and prevention of malaria and toxoplasmosis. ...Cytochrome , a dimeric multi-subunit electron-transport protein embedded in the inner mitochondrial membrane, is a major drug target for the treatment and prevention of malaria and toxoplasmosis. Structural studies of cytochrome from mammalian homologues co-crystallized with lead compounds have underpinned structure-based drug design to develop compounds with higher potency and selectivity. However, owing to the limited amount of cytochrome that may be available from parasites, all efforts have been focused on homologous cytochrome complexes from mammalian species, which has resulted in the failure of some drug candidates owing to toxicity in the host. Crystallographic studies of the native parasite proteins are not feasible owing to limited availability of the proteins. Here, it is demonstrated that cytochrome is highly amenable to single-particle cryo-EM (which uses significantly less protein) by solving the apo and two inhibitor-bound structures to ∼4.1 Å resolution, revealing clear inhibitor density at the binding site. Therefore, cryo-EM is proposed as a viable alternative method for structure-based drug discovery using both host and parasite enzymes. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_4292.map.gz | 21 MB | EMDB map data format | |
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Header (meta data) | emd-4292-v30.xml emd-4292.xml | 30 KB 30 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_4292_fsc.xml | 6.9 KB | Display | FSC data file |
Images | emd_4292.png | 76.4 KB | ||
Others | emd_4292_additional.map.gz emd_4292_half_map_1.map.gz emd_4292_half_map_2.map.gz | 22.5 MB 12.4 MB 12.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-4292 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-4292 | HTTPS FTP |
-Validation report
Summary document | emd_4292_validation.pdf.gz | 389.5 KB | Display | EMDB validaton report |
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Full document | emd_4292_full_validation.pdf.gz | 388.7 KB | Display | |
Data in XML | emd_4292_validation.xml.gz | 12.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4292 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4292 | HTTPS FTP |
-Related structure data
Related structure data | 6fo6MC 4286C 4288C 5okdC 6fo0C 6fo2C C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_4292.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | The cryoEM map of bovine cytochrome bc1 in complex with the anti-malarial inhibitor SCR0911 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.067 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: The unsharpened map for SCR0911-bound bc1.
File | emd_4292_additional.map | ||||||||||||
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Annotation | The unsharpened map for SCR0911-bound bc1. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: The first half map for SCR0911-bound bc1.
File | emd_4292_half_map_1.map | ||||||||||||
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Annotation | The first half map for SCR0911-bound bc1. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: A second map for SCR0911-bound bc1.
File | emd_4292_half_map_2.map | ||||||||||||
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Annotation | A second map for SCR0911-bound bc1. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Cytochrome bc1 in complex with the antimalarial inhibitor SCR0911
+Supramolecule #1: Cytochrome bc1 in complex with the antimalarial inhibitor SCR0911
+Macromolecule #1: Cytochrome b-c1 complex subunit Rieske, mitochondrial
+Macromolecule #2: Cytochrome b-c1 complex subunit 1, mitochondrial
+Macromolecule #3: Cytochrome b-c1 complex subunit 2, mitochondrial
+Macromolecule #4: Cytochrome b
+Macromolecule #5: Cytochrome c1, heme protein, mitochondrial
+Macromolecule #6: Cytochrome b-c1 complex subunit 7
+Macromolecule #7: Cytochrome b-c1 complex subunit 8
+Macromolecule #8: Cytochrome b-c1 complex subunit 6, mitochondrial
+Macromolecule #9: Cytochrome b-c1 complex subunit 9
+Macromolecule #10: PROTOPORPHYRIN IX CONTAINING FE
+Macromolecule #11: 7-methoxy-3-methyl-2-[5-[4-(trifluoromethyloxy)phenyl]pyridin-3-y...
+Macromolecule #12: HEME C
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 5.0 mg/mL | |||||||||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Pretreatment - Type: GLOW DISCHARGE | |||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV Details: blot for 6 seconds with a blot force of 6 before plunge-freezing. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: INTEGRATING / Number grids imaged: 1 / Number real images: 7893 / Average exposure time: 2.0 sec. / Average electron dose: 85.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 4.0 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 79000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: FLEXIBLE FIT |
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Output model | PDB-6fo6: |