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Yorodumi- PDB-4ke1: Crystal structure of BACE1 in complex with hydroxyethylamine-macr... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4ke1 | ||||||
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Title | Crystal structure of BACE1 in complex with hydroxyethylamine-macrocyclic inhibitor 19 | ||||||
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 / prepulse inhibition / detection of mechanical stimulus involved in sensory perception of pain ...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 / prepulse inhibition / detection of mechanical stimulus involved in sensory perception of pain / amyloid-beta metabolic process / cellular response to copper ion / hippocampal mossy fiber to CA3 synapse / presynaptic modulation of chemical synaptic transmission / multivesicular body / response to lead ion / trans-Golgi network / protein processing / recycling endosome / cellular response to amyloid-beta / positive regulation of neuron apoptotic process / synaptic vesicle / late endosome / amyloid-beta binding / peptidase activity / endopeptidase activity / amyloid fibril formation / lysosome / aspartic-type endopeptidase activity / early endosome / endosome membrane / endosome / membrane raft / Amyloid fiber formation / axon / endoplasmic reticulum lumen / 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: 1.91 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 | 4ke1.cif.gz | 160.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4ke1.ent.gz | 132.8 KB | Display | PDB format |
PDBx/mmJSON format | 4ke1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ke/4ke1 ftp://data.pdbj.org/pub/pdb/validation_reports/ke/4ke1 | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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Components on special symmetry positions |
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-Components
#1: Protein | Mass: 45822.445 Da / Num. of mol.: 1 / Fragment: UNP residues 43-453 / Mutation: R56K, R57K Source method: isolated from a genetically manipulated source Details: refolded from inclusion bodies / Source: (gene. exp.) Homo sapiens (human) / Gene: BACE1, BACE, KIAA1149 / Production host: Escherichia coli (E. coli) / References: UniProt: P56817, memapsin 2 | ||||||
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#2: Chemical | #3: Chemical | ChemComp-1R6 / ( | #4: Chemical | ChemComp-GOL / | #5: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.8 Å3/Da / Density % sol: 56.13 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 6.6 Details: 21% PEG 5000 MME, 0.2 M sodium citrate, 0.2 M ammonium iodide, pH 6.6, VAPOR DIFFUSION, HANGING DROP, temperature 298K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 31-ID / Wavelength: 0.9793 Å |
Detector | Type: MAR CCD 165 mm / Detector: CCD / Date: Nov 14, 2007 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9793 Å / Relative weight: 1 |
Reflection | Resolution: 1.91→28.27 Å / Num. all: 41621 / Num. obs: 41330 / % possible obs: 99.3 % / Redundancy: 14.1 % / Biso Wilson estimate: 28.9 Å2 / Rmerge(I) obs: 0.084 / Net I/σ(I): 16.9 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS / Resolution: 1.91→28.27 Å / Cor.coef. Fo:Fc: 0.94 / Cor.coef. Fo:Fc free: 0.923 / WRfactor Rfree: 0.2624 / WRfactor Rwork: 0.2269 / Occupancy max: 1 / Occupancy min: 0.5 / FOM work R set: 0.8561 / SU B: 6.015 / SU ML: 0.099 / SU R Cruickshank DPI: 0.142 / SU Rfree: 0.1344 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.142 / ESU R Free: 0.134 / 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: 183.1 Å2 / Biso mean: 44.5491 Å2 / Biso min: 13.43 Å2
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Refinement step | Cycle: LAST / Resolution: 1.91→28.27 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.912→1.961 Å / 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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