+Open data
-Basic information
Entry | Database: PDB / ID: 7lrl | ||||||
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Title | Co-complex CYP46A1 with 7742 (Soticlestat/TAK-935)) | ||||||
Components | Cholesterol 24-hydroxylase | ||||||
Keywords | HYDROLASE / cyp46a1 / ch24h / sbdd / drug discovery | ||||||
Function / homology | Function and homology information cholesterol 24-hydroxylase / cholesterol 24-hydroxylase activity / protein localization to membrane raft / testosterone 16-beta-hydroxylase activity / Synthesis of bile acids and bile salts via 24-hydroxycholesterol / progesterone metabolic process / sterol metabolic process / bile acid biosynthetic process / regulation of long-term synaptic potentiation / steroid hydroxylase activity ...cholesterol 24-hydroxylase / cholesterol 24-hydroxylase activity / protein localization to membrane raft / testosterone 16-beta-hydroxylase activity / Synthesis of bile acids and bile salts via 24-hydroxycholesterol / progesterone metabolic process / sterol metabolic process / bile acid biosynthetic process / regulation of long-term synaptic potentiation / steroid hydroxylase activity / cholesterol catabolic process / Endogenous sterols / xenobiotic metabolic process / presynapse / nervous system development / postsynapse / iron ion binding / dendrite / heme binding / endoplasmic reticulum membrane / endoplasmic reticulum Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.995 Å | ||||||
Authors | Lane, W. / Yano, J. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2021 Title: Discovery of Soticlestat, a Potent and Selective Inhibitor for Cholesterol 24-Hydroxylase (CH24H). Authors: Koike, T. / Yoshikawa, M. / Ando, H.K. / Farnaby, W. / Nishi, T. / Watanabe, E. / Yano, J. / Miyamoto, M. / Kondo, S. / Ishii, T. / Kuroita, T. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7lrl.cif.gz | 111.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7lrl.ent.gz | 80.3 KB | Display | PDB format |
PDBx/mmJSON format | 7lrl.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/lr/7lrl ftp://data.pdbj.org/pub/pdb/validation_reports/lr/7lrl | HTTPS FTP |
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-Related structure data
Related structure data | 7ls3C 7ls4C 2q9gS 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
#1: Protein | Mass: 54434.723 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CYP46A1, CYP46 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9Y6A2, cholesterol 24-hydroxylase |
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#2: Chemical | ChemComp-HEM / |
#3: Chemical | ChemComp-YBS / [ |
#4: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.1 Å3/Da / Density % sol: 41.51 % |
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Crystal grow | Temperature: 293.15 K / Method: vapor diffusion, sitting drop / Details: 18.5% PEG 3350, 0.4M Calcium Cl |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 0.976 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Sep 7, 2011 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.976 Å / Relative weight: 1 |
Reflection | Resolution: 1.995→35.3 Å / Num. obs: 31636 / % possible obs: 98.8 % / Redundancy: 5.9 % / Rsym value: 0.126 / Net I/σ(I): 12.6 |
Reflection shell | Resolution: 1.995→2.03 Å / Mean I/σ(I) obs: 1.9 / Num. unique obs: 1293 / Rsym value: 0.609 / % possible all: 83.2 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2Q9G Resolution: 1.995→35.272 Å / Cor.coef. Fo:Fc: 0.936 / Cor.coef. Fo:Fc free: 0.932 / Cross valid method: FREE R-VALUE / ESU R: 0.226 / ESU R Free: 0.171 / Details: Hydrogens have not been used
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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 BULK SOLVENT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 16.735 Å2
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Refinement step | Cycle: LAST / Resolution: 1.995→35.272 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20
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