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Yorodumi- PDB-6btl: Crystal structure of Trypanothione Reductase from Trypanosoma bru... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6btl | |||||||||||||||||||||
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Title | Crystal structure of Trypanothione Reductase from Trypanosoma brucei in complex with inhibitor RD117 1-[2-(Piperazin-1-yl)ethyl]-5-{5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl}-1H-indole | |||||||||||||||||||||
Components | Trypanothione reductase | |||||||||||||||||||||
Keywords | OXIDOREDUCTASE/Inhibitor / Inhibitor / Complex / Sleeping Sickness / OXIDOREDUCTASE-Inhibitor complex | |||||||||||||||||||||
Function / homology | Function and homology information trypanothione-disulfide reductase / trypanothione-disulfide reductase (NADPH) activity / glutathione-disulfide reductase (NADPH) activity / glycosome / thioredoxin-disulfide reductase (NADPH) activity / ciliary plasm / glutathione metabolic process / cell redox homeostasis / flavin adenine dinucleotide binding / cellular response to oxidative stress ...trypanothione-disulfide reductase / trypanothione-disulfide reductase (NADPH) activity / glutathione-disulfide reductase (NADPH) activity / glycosome / thioredoxin-disulfide reductase (NADPH) activity / ciliary plasm / glutathione metabolic process / cell redox homeostasis / flavin adenine dinucleotide binding / cellular response to oxidative stress / mitochondrion / nucleoplasm / metal ion binding / cytoplasm / cytosol Similarity search - Function | |||||||||||||||||||||
Biological species | Trypanosoma brucei brucei TREU927 (eukaryote) | |||||||||||||||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.797 Å | |||||||||||||||||||||
Authors | Bryson, S. / De Gasparo, R. / Krauth-Siegel, R.L. / Diederich, F. / Pai, E.F. | |||||||||||||||||||||
Funding support | Canada, Switzerland, Germany, United States, 6items
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Citation | Journal: ChemMedChem / Year: 2018 Title: Biological Evaluation and X-ray Co-crystal Structures of Cyclohexylpyrrolidine Ligands for Trypanothione Reductase, an Enzyme from the Redox Metabolism of Trypanosoma. Authors: De Gasparo, R. / Brodbeck-Persch, E. / Bryson, S. / Hentzen, N.B. / Kaiser, M. / Pai, E.F. / Krauth-Siegel, R.L. / Diederich, F. #1: Journal: ChemMedChem / Year: 2014 Title: Binding to large enzyme pockets: small-molecule inhibitors of trypanothione reductase. Authors: Persch, E. / Bryson, S. / Todoroff, N.K. / Eberle, C. / Thelemann, J. / Dirdjaja, N. / Kaiser, M. / Weber, M. / Derbani, H. / Brun, R. / Schneider, G. / Pai, E.F. / Krauth-Siegel, R.L. / Diederich, F. | |||||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6btl.cif.gz | 408.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6btl.ent.gz | 333.1 KB | Display | PDB format |
PDBx/mmJSON format | 6btl.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6btl_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 6btl_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 6btl_validation.xml.gz | 39.8 KB | Display | |
Data in CIF | 6btl_validation.cif.gz | 52.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/bt/6btl ftp://data.pdbj.org/pub/pdb/validation_reports/bt/6btl | HTTPS FTP |
-Related structure data
Related structure data | 6bu7C 2woiS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
-Protein , 1 types, 2 molecules AB
#1: Protein | Mass: 53497.969 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Trypanosoma brucei brucei TREU927 (eukaryote) Strain: 927/4 GUTat10.1 / Gene: Tb10.406.0520 / Production host: Escherichia coli (E. coli) References: UniProt: Q389T8, trypanothione-disulfide reductase |
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-Non-polymers , 6 types, 24 molecules
#2: Chemical | #3: Chemical | ChemComp-SO4 / #4: Chemical | #5: Chemical | ChemComp-GOL / #6: Chemical | #7: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.66 Å3/Da / Density % sol: 66.4 % |
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Crystal grow | Temperature: 294 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: Adding 5 microL of 10 mM inhibitor in DMSO to 95 microL of protein solution (10mg/ml; 20 mM TRIS, pH8.0), then mixing 2 microL of protein solution with 2 microL of well solution (0.1 M ...Details: Adding 5 microL of 10 mM inhibitor in DMSO to 95 microL of protein solution (10mg/ml; 20 mM TRIS, pH8.0), then mixing 2 microL of protein solution with 2 microL of well solution (0.1 M HEPES, pH 7.5, 2.0 M (NH4)2SO4). |
-Data collection
Diffraction | Mean temperature: 93 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 23-ID-D / Wavelength: 1.0332 Å |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Dec 3, 2016 / Details: collimator |
Radiation | Monochromator: double crystal monochromator and K-B pair of bimorph mirrors for vertical and horizontal focusing Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.0332 Å / Relative weight: 1 |
Reflection | Resolution: 2.797→47.7 Å / Num. obs: 39719 / % possible obs: 99.4 % / Redundancy: 8.6 % / Biso Wilson estimate: 79.3 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.137 / Rpim(I) all: 0.049 / Rrim(I) all: 0.146 / Net I/σ(I): 16.8 |
Reflection shell | Resolution: 2.797→2.9 Å / Redundancy: 7.2 % / Rmerge(I) obs: 1.609 / Num. unique obs: 3684 / CC1/2: 0.423 / Rpim(I) all: 0.618 / Rrim(I) all: 1.728 / % possible all: 95 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2WOI Resolution: 2.797→47.671 Å / SU ML: 0.4 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 27.28 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.797→47.671 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: 31.965 Å / Origin y: -13.1127 Å / Origin z: 6.9945 Å
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Refinement TLS group | Selection details: all |