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Open data
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Basic information
Entry | Database: PDB / ID: 4xry | ||||||
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Title | Human Cytochrome P450 2D6 BACE1 Inhibitor 5 Complex | ||||||
![]() | Cytochrome P450 2D6 | ||||||
![]() | OXIDOREDUCTASE / CYP2D6 / P450 2D6 / Cytochrome P450 / MONOOXYGENASE / BACE1 | ||||||
Function / homology | ![]() negative regulation of binding / negative regulation of cellular 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 / arachidonic acid metabolic process / anandamide 8,9 epoxidase activity ...negative regulation of binding / negative regulation of cellular 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 / arachidonic acid metabolic process / anandamide 8,9 epoxidase activity / anandamide 11,12 epoxidase activity / anandamide 14,15 epoxidase activity / alkaloid catabolic process / alkaloid metabolic process / Biosynthesis of maresin-like SPMs / monoterpenoid 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 / monooxygenase activity / cholesterol metabolic process / xenobiotic metabolic process / oxidoreductase activity / iron ion binding / intracellular membrane-bounded organelle / heme binding / endoplasmic reticulum membrane / endoplasmic reticulum / mitochondrion / cytoplasm Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Johnson, E.F. / Fan, Y. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Utilizing Structures of CYP2D6 and BACE1 Complexes To Reduce Risk of Drug-Drug Interactions with a Novel Series of Centrally Efficacious BACE1 Inhibitors. Authors: Brodney, M.A. / Beck, E.M. / Butler, C.R. / Barreiro, G. / Johnson, E.F. / Riddell, D. / Parris, K. / Nolan, C.E. / Fan, Y. / Atchison, K. / Gonzales, C. / Robshaw, A.E. / Doran, S.D. / ...Authors: Brodney, M.A. / Beck, E.M. / Butler, C.R. / Barreiro, G. / Johnson, E.F. / Riddell, D. / Parris, K. / Nolan, C.E. / Fan, Y. / Atchison, K. / Gonzales, C. / Robshaw, A.E. / Doran, S.D. / Bundesmann, M.W. / Buzon, L. / Dutra, J. / Henegar, K. / LaChapelle, E. / Hou, X. / Rogers, B.N. / Pandit, J. / Lira, R. / Martinez-Alsina, L. / Mikochik, P. / Murray, J.C. / Ogilvie, K. / Price, L. / Sakya, S.M. / Yu, A. / Zhang, Y. / O'Neill, B.T. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 376.1 KB | Display | ![]() |
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PDB format | ![]() | 305.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 2.7 MB | Display | ![]() |
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Full document | ![]() | 2.7 MB | Display | |
Data in XML | ![]() | 65 KB | Display | |
Data in CIF | ![]() | 86.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 4xrzC ![]() 4xxsC ![]() 3tbgS C: citing same article ( S: Starting model for refinement |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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4 | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 53730.566 Da / Num. of mol.: 4 / Fragment: UNP residues 34-497 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Chemical | ChemComp-HEM / #3: Chemical | ChemComp-SI5 / ( #4: Chemical | ChemComp-ZN / #5: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 3.16 Å3/Da / Density % sol: 61.04 % |
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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. Beta- ...Details: PEG3350, SODIUM ACETATE, SODIUM CACODYLATE, POTASSIUM PHOSPHATE, SODIUM CHLORIDE, ZINC CHLORIDE, GLYCEROL, BETA-MERCAPTOETHANOL, THIORIDAZINE, HEGA-10, FACIAL AMPHIPHILE 231_CHOL. Beta-secretase inhibitor was added to the mother liquor after crystallization of the P450 2D6 thiordidazine ternary complex. |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: May 25, 2013 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 |
Reflection | Resolution: 2.5→39.16 Å / Num. obs: 95062 / % possible obs: 99.6 % / Redundancy: 6.6 % / Biso Wilson estimate: 46.49 Å2 / Rmerge(I) obs: 0.047 / Net I/σ(I): 27.8 |
Reflection shell | Resolution: 2.5→2.54 Å / Redundancy: 6.9 % / Rmerge(I) obs: 0.397 / Mean I/σ(I) obs: 5.2 / % possible all: 99.9 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 3TBG Resolution: 2.5→39.16 Å / SU ML: 0.3 / Cross valid method: THROUGHOUT / σ(F): 1.08 / Phase error: 27.8 / 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 mean: 55.8 Å2 | ||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.5→39.16 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.5→2.54 Å / Rfactor Rfree: 0.2995 / Rfactor Rwork: 0.2538 |