+Open data
-Basic information
Entry | Database: PDB / ID: 7ls4 | ||||||
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Title | Co-complex CYP46A1 with 9129 (1b) | ||||||
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 / molecular replacement / Resolution: 2.05 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 | 7ls4.cif.gz | 197.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7ls4.ent.gz | 153.3 KB | Display | PDB format |
PDBx/mmJSON format | 7ls4.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ls/7ls4 ftp://data.pdbj.org/pub/pdb/validation_reports/ls/7ls4 | HTTPS FTP |
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-Related structure data
Related structure data | 7lrlC 7ls3C 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-YCG / [ |
#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: 2.13 Å3/Da / Density % sol: 42.13 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / Details: 33.375% PEG MME 2000, 0.2M Mg Cl, 0.1M Tris Cl |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 23-ID-B / Wavelength: 0.979 Å |
Detector | Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Oct 9, 2008 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.979 Å / Relative weight: 1 |
Reflection | Resolution: 2.05→35 Å / Num. obs: 28194 / % possible obs: 99.9 % / Redundancy: 6.8 % / Rsym value: 0.12 / Net I/σ(I): 17.7 |
Reflection shell | Resolution: 2.05→2.1 Å / Mean I/σ(I) obs: 1.9 / Num. unique obs: 1945 / Rsym value: 0.727 / % possible all: 99.4 |
-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2Q9G Resolution: 2.05→29.8 Å / Cor.coef. Fo:Fc: 0.962 / Cor.coef. Fo:Fc free: 0.936 / SU B: 10.385 / SU ML: 0.144 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.208 / ESU R Free: 0.179 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: U VALUES : WITH TLS ADDED
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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 max: 119.49 Å2 / Biso mean: 41.026 Å2 / Biso min: 18.79 Å2
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Refinement step | Cycle: final / Resolution: 2.05→29.8 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.052→2.105 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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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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