+Open data
-Basic information
Entry | Database: PDB / ID: 4wnt | ||||||
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Title | Human Cytochrome P450 2D6 Ajmalicine Complex | ||||||
Components | Cytochrome P450 2D6 | ||||||
Keywords | oxidoreductase/oxidoreductase inhibitor / CYP2D6 / P450 2D6 / Cytochrome P450 / MONOOXYGENASE / oxidoreductase-oxidoreductase inhibitor complex | ||||||
Function / homology | Function and homology information negative regulation of binding / negative regulation of organofluorine metabolic process / Miscellaneous substrates / isoquinoline alkaloid metabolic process / Fatty acids / coumarin metabolic process / Oxidoreductases; Acting on paired donors, with incorporation or reduction of molecular oxygen; With reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen into the other donor / CYP2E1 reactions / arachidonate metabolic process / anandamide 8,9 epoxidase activity ...negative regulation of binding / negative regulation of organofluorine metabolic process / Miscellaneous substrates / isoquinoline alkaloid metabolic process / Fatty acids / coumarin metabolic process / Oxidoreductases; Acting on paired donors, with incorporation or reduction of molecular oxygen; With reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen into the other donor / CYP2E1 reactions / arachidonate metabolic process / anandamide 8,9 epoxidase activity / anandamide 11,12 epoxidase activity / anandamide 14,15 epoxidase activity / alkaloid catabolic process / Biosynthesis of maresin-like SPMs / monoterpenoid metabolic process / alkaloid metabolic process / oxidative demethylation / Xenobiotics / oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen / long-chain fatty acid biosynthetic process / estrogen metabolic process / retinol metabolic process / Aspirin ADME / steroid metabolic process / xenobiotic catabolic process / xenobiotic metabolic process / cholesterol metabolic process / monooxygenase activity / oxidoreductase activity / iron ion binding / intracellular membrane-bounded organelle / heme binding / endoplasmic reticulum membrane / endoplasmic reticulum / mitochondrion / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.6 Å | ||||||
Authors | Wang, A. / Stout, C.D. / Johnson, E.F. | ||||||
Funding support | United States, 1items
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Citation | Journal: J.Biol.Chem. / Year: 2015 Title: Contributions of Ionic Interactions and Protein Dynamics to Cytochrome P450 2D6 (CYP2D6) Substrate and Inhibitor Binding. Authors: Wang, A. / Stout, C.D. / Zhang, Q. / Johnson, E.F. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4wnt.cif.gz | 380.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4wnt.ent.gz | 310.7 KB | Display | PDB format |
PDBx/mmJSON format | 4wnt.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4wnt_validation.pdf.gz | 1.7 MB | Display | wwPDB validaton report |
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Full document | 4wnt_full_validation.pdf.gz | 1.7 MB | Display | |
Data in XML | 4wnt_validation.xml.gz | 34.7 KB | Display | |
Data in CIF | 4wnt_validation.cif.gz | 46.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wn/4wnt ftp://data.pdbj.org/pub/pdb/validation_reports/wn/4wnt | HTTPS FTP |
-Related structure data
Related structure data | 3tbgC 3tdaSC 4wnuC 4wnvC 4wnwC C: citing same article (ref.) S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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2 |
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Unit cell |
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Components on special symmetry positions |
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Details | monomeric |
-Components
#1: Protein | Mass: 53730.566 Da / Num. of mol.: 2 / Fragment: UNP RESIDUES 34-497 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CYP2D6, CYP2DL1 / Plasmid: PCWORI / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): DH5ALPHA / References: UniProt: P10635, unspecific monooxygenase #2: Chemical | #3: Chemical | #4: Chemical | #5: 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: 3.24 Å3/Da / Density % sol: 62.06 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop Details: PEG3350, SODIUM ACETATE, SODIUM CACODYLATE, POTASSIUM PHOSPHATE, SODIUM CHLORIDE, ZINC CHLORIDE, GLYCEROL, BETA-MERCAPTOETHANOL, THIORIDAZINE, HEGA-10, FACIAL AMPHIPHILE 231_CHOL. Ajmalicine ...Details: PEG3350, SODIUM ACETATE, SODIUM CACODYLATE, POTASSIUM PHOSPHATE, SODIUM CHLORIDE, ZINC CHLORIDE, GLYCEROL, BETA-MERCAPTOETHANOL, THIORIDAZINE, HEGA-10, FACIAL AMPHIPHILE 231_CHOL. Ajmalicine was added to the mother liquor after crystallization of the P450 2D6 thiordidazine complex. |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: SSRL / Beamline: BL7-1 / Wavelength: 1.097173 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Jul 25, 2011 / Details: Rh coated flat mirror | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Monochromator: Side scattering bent cube-root I-beam single crystal Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1.097173 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.6→45.012 Å / Num. all: 42976 / Num. obs: 42976 / % possible obs: 98 % / Redundancy: 3.2 % / Biso Wilson estimate: 45.88 Å2 / Rmerge(I) obs: 0.073 / Rpim(I) all: 0.047 / Rrim(I) all: 0.087 / Rsym value: 0.073 / Net I/av σ(I): 8 / Net I/σ(I): 10.8 / Num. measured all: 138204 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1 / Rejects: _
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3TDA Resolution: 2.6→42.667 Å / SU ML: 0.29 / Cross valid method: THROUGHOUT / σ(F): 0 / Phase error: 24.01 / 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 155 Å2 / Biso mean: 59.9193 Å2 / Biso min: 22.45 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.6→42.667 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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