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Yorodumi- PDB-4ke0: Crystal structure of BACE1 in complex with hydroxyethylamine-macr... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4ke0 | ||||||
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Title | Crystal structure of BACE1 in complex with hydroxyethylamine-macrocyclic inhibitor 13 | ||||||
Components | Beta-secretase 1 | ||||||
Keywords | HYDROLASE/HYDROLASE INHIBITOR / Alzheimer's disease / aspartic protease / amyloid precursor protein (APP) / HYDROLASE-HYDROLASE INHIBITOR complex | ||||||
Function / homology | Function and homology information memapsin 2 / Golgi-associated vesicle lumen / signaling receptor ligand precursor processing / beta-aspartyl-peptidase activity / amyloid precursor protein catabolic process / amyloid-beta formation / membrane protein ectodomain proteolysis / cellular response to manganese ion / amyloid-beta metabolic process / prepulse inhibition ...memapsin 2 / Golgi-associated vesicle lumen / signaling receptor ligand precursor processing / beta-aspartyl-peptidase activity / amyloid precursor protein catabolic process / amyloid-beta formation / membrane protein ectodomain proteolysis / cellular response to manganese ion / amyloid-beta metabolic process / prepulse inhibition / detection of mechanical stimulus involved in sensory perception of pain / cellular response to copper ion / presynaptic modulation of chemical synaptic transmission / hippocampal mossy fiber to CA3 synapse / multivesicular body / response to lead ion / trans-Golgi network / recycling endosome / protein processing / cellular response to amyloid-beta / positive regulation of neuron apoptotic process / synaptic vesicle / late endosome / peptidase activity / amyloid-beta binding / endopeptidase activity / amyloid fibril formation / lysosome / aspartic-type endopeptidase activity / early endosome / endosome membrane / endosome / membrane raft / Amyloid fiber formation / endoplasmic reticulum lumen / axon / neuronal cell body / dendrite / Golgi apparatus / enzyme binding / cell surface / proteolysis / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.3 Å | ||||||
Authors | Whittington, D.A. / Long, A.M. / Li, V. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2013 Title: Hydroxyethylamine-based inhibitors of BACE1: P1-P3 macrocyclization can improve potency, selectivity, and cell activity. Authors: Pennington, L.D. / Whittington, D.A. / Bartberger, M.D. / Jordan, S.R. / Monenschein, H. / Nguyen, T.T. / Yang, B.H. / Xue, Q.M. / Vounatsos, F. / Wahl, R.C. / Chen, K. / Wood, S. / Citron, ...Authors: Pennington, L.D. / Whittington, D.A. / Bartberger, M.D. / Jordan, S.R. / Monenschein, H. / Nguyen, T.T. / Yang, B.H. / Xue, Q.M. / Vounatsos, F. / Wahl, R.C. / Chen, K. / Wood, S. / Citron, M. / Patel, V.F. / Hitchcock, S.A. / Zhong, W. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4ke0.cif.gz | 238 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4ke0.ent.gz | 199.7 KB | Display | PDB format |
PDBx/mmJSON format | 4ke0.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ke/4ke0 ftp://data.pdbj.org/pub/pdb/validation_reports/ke/4ke0 | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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3 |
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Unit cell |
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-Components
#1: Protein | Mass: 45822.445 Da / Num. of mol.: 3 / Fragment: UNP residues 43-454 / Mutation: R56K, R57K Source method: isolated from a genetically manipulated source Details: refolded from inclusion bodies / Source: (gene. exp.) Homo sapiens (human) / Gene: BACE, BACE1, KIAA1149 / Production host: Escherichia coli (E. coli) / References: UniProt: P56817, memapsin 2 #2: Chemical | #3: Chemical | #4: Chemical | ChemComp-SO4 / | #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: 3.01 Å3/Da / Density % sol: 59.2 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 5 Details: 18% PEG 8000, 0.3 M lithium sulfate, 0.1 M sodium citrate, pH 5.0, VAPOR DIFFUSION, HANGING DROP, temperature 298K |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Oct 27, 2011 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Monochromator: Double-crystal, Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.3→50 Å / Num. all: 72557 / Num. obs: 72412 / % possible obs: 99.8 % / Observed criterion σ(I): -3 / Redundancy: 3.8 % / Biso Wilson estimate: 56.5 Å2 / Rmerge(I) obs: 0.082 / Χ2: 1.523 / Net I/σ(I): 16.1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS / Resolution: 2.3→44 Å / Cor.coef. Fo:Fc: 0.969 / Cor.coef. Fo:Fc free: 0.954 / WRfactor Rfree: 0.2078 / WRfactor Rwork: 0.1707 / Occupancy max: 1 / Occupancy min: 1 / FOM work R set: 0.8539 / SU B: 5.362 / SU ML: 0.129 / SU R Cruickshank DPI: 0.2205 / SU Rfree: 0.1802 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.22 / ESU R Free: 0.18 / Stereochemistry target values: MAXIMUM LIKELIHOOD
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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: 149.39 Å2 / Biso mean: 56.7678 Å2 / Biso min: 29.47 Å2
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Refinement step | Cycle: LAST / Resolution: 2.3→44 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.3→2.36 Å / Total num. of bins used: 20
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