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- PDB-5okd: Crystal structure of bovine Cytochrome bc1 in complex with inhibi... -
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Open data
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Basic information
Entry | Database: PDB / ID: 5okd | |||||||||
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Title | Crystal structure of bovine Cytochrome bc1 in complex with inhibitor SCR0911. | |||||||||
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![]() | ELECTRON TRANSPORT / antimalarial inhibitor / Qi site binder | |||||||||
Function / homology | ![]() Respiratory electron transport / : / quinol-cytochrome-c reductase / ubiquinol-cytochrome-c reductase activity / mitochondrial electron transport, ubiquinol to cytochrome c / Mitochondrial protein degradation / : / ubiquinone binding / respiratory electron transport chain / mitochondrial membrane ...Respiratory electron transport / : / quinol-cytochrome-c reductase / ubiquinol-cytochrome-c reductase activity / mitochondrial electron transport, ubiquinol to cytochrome c / Mitochondrial protein degradation / : / ubiquinone binding / 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 / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Amporndanai, K. / O'Neill, P.M. / Hasnain, S.S. / Antonyuk, S.V. | |||||||||
![]() | ![]() 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
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 861 KB | Display | ![]() |
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PDB format | ![]() | 699.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 3.6 MB | Display | ![]() |
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Full document | ![]() | 3.7 MB | Display | |
Data in XML | ![]() | 74.9 KB | Display | |
Data in CIF | ![]() | 100 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 4286C ![]() 4288C ![]() 4292C ![]() 6fo0C ![]() 6fo2C ![]() 6fo6C ![]() 4d6tS S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components on special symmetry positions |
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Components
-Cytochrome b-c1 complex subunit ... , 8 types, 8 molecules ABEFGHIJ
#1: Protein | Mass: 52840.461 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#2: Protein | Mass: 48203.434 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#5: Protein | Mass: 21640.580 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#6: Protein | Mass: 13502.387 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#7: Protein | Mass: 9737.223 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#8: Protein | Mass: 10638.744 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#9: Protein/peptide | Mass: 4898.645 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#10: Protein | Mass: 7469.621 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-Protein , 2 types, 2 molecules CD
#3: Protein | Mass: 42620.340 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#4: Protein | Mass: 35343.770 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-Sugars , 1 types, 1 molecules ![](data/chem/img/LMT.gif)
#16: Sugar | ChemComp-LMT / |
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-Non-polymers , 11 types, 104 molecules ![](data/chem/img/PG4.gif)
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![](data/chem/img/FES.gif)
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![](data/chem/img/HOH.gif)
![](data/chem/img/6PE.gif)
![](data/chem/img/CDL.gif)
![](data/chem/img/HEM.gif)
![](data/chem/img/9XE.gif)
![](data/chem/img/PEE.gif)
![](data/chem/img/HEC.gif)
![](data/chem/img/PO4.gif)
![](data/chem/img/FES.gif)
![](data/chem/img/PX4.gif)
![](data/chem/img/HOH.gif)
#11: Chemical | #12: Chemical | ChemComp-6PE / | #13: Chemical | ChemComp-CDL / #14: Chemical | #15: Chemical | ChemComp-9XE / | #17: Chemical | #18: Chemical | ChemComp-HEC / | #19: Chemical | ChemComp-PO4 / #20: Chemical | ChemComp-FES / | #21: Chemical | ChemComp-PX4 / | #22: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 4.41 Å3/Da / Density % sol: 72.08 % / Description: Bipyramidal red |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop Details: Protein 40mg/mL with 1.6% HECAMEG; reservoir solution 50mM KPi pH 6.8, 100mM NaCl, 3mM NaN3, 10-13% PEG4000 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Feb 27, 2017 / Details: mirrors |
Radiation | Monochromator: Si111 / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 3.1→89 Å / Num. obs: 80268 / % possible obs: 99.5 % / Redundancy: 7.4 % / Biso Wilson estimate: 71.303 Å2 / CC1/2: 0.977 / Rmerge(I) obs: 0.104 / Rpim(I) all: 0.043 / Net I/σ(I): 12.3 |
Reflection shell | Resolution: 3.1→3.16 Å / Redundancy: 7.5 % / Rmerge(I) obs: 1.126 / Mean I/σ(I) obs: 1.8 / Num. unique obs: 4428 / CC1/2: 0.572 / Rpim(I) all: 0.655 / % possible all: 99.9 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 4d6t Resolution: 3.1→31.76 Å / Cor.coef. Fo:Fc: 0.936 / Cor.coef. Fo:Fc free: 0.915 / SU B: 37.897 / SU ML: 0.295 / Cross valid method: THROUGHOUT / ESU R: 0.821 / ESU R Free: 0.353 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 101.1 Å2
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Refinement step | Cycle: 1 / Resolution: 3.1→31.76 Å
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