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Yorodumi- PDB-4r5n: 8-Tetrahydropyran-2-yl chromans: highly selective beta-site amylo... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4r5n | ||||||
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Title | 8-Tetrahydropyran-2-yl chromans: highly selective beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors | ||||||
Components | Beta-secretase 1 | ||||||
Keywords | hydrolase/hydrolase inhibitor / aspartyl protease / 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 / protein serine/threonine kinase binding / 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 / protein processing / recycling endosome / 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 / aspartic-type endopeptidase activity / lysosome / 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 / MOLECULAR REPLACEMENT / Resolution: 1.8 Å | ||||||
Authors | Vigers, G.P.A. / Smith, D. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2014 Title: 8-Tetrahydropyran-2-yl Chromans: Highly Selective Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitors. Authors: Thomas, A.A. / Hunt, K.W. / Newhouse, B. / Watts, R.J. / Liu, X. / Vigers, G. / Smith, D. / Rhodes, S.P. / Brown, K.D. / Otten, J.N. / Burkard, M. / Cox, A.A. / Geck Do, M.K. / Dutcher, D. / ...Authors: Thomas, A.A. / Hunt, K.W. / Newhouse, B. / Watts, R.J. / Liu, X. / Vigers, G. / Smith, D. / Rhodes, S.P. / Brown, K.D. / Otten, J.N. / Burkard, M. / Cox, A.A. / Geck Do, M.K. / Dutcher, D. / Rana, S. / DeLisle, R.K. / Regal, K. / Wright, A.D. / Groneberg, R. / Liao, J. / Scearce-Levie, K. / Siu, M. / Purkey, H.E. / Lyssikatos, J.P. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4r5n.cif.gz | 100.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4r5n.ent.gz | 74 KB | Display | PDB format |
PDBx/mmJSON format | 4r5n.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4r5n_validation.pdf.gz | 767.8 KB | Display | wwPDB validaton report |
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Full document | 4r5n_full_validation.pdf.gz | 771.6 KB | Display | |
Data in XML | 4r5n_validation.xml.gz | 19.1 KB | Display | |
Data in CIF | 4r5n_validation.cif.gz | 28.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/r5/4r5n ftp://data.pdbj.org/pub/pdb/validation_reports/r5/4r5n | HTTPS FTP |
-Related structure data
Related structure data | 4rrnC 4rroC 4rrsC 4n00S 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 on special symmetry positions |
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-Components
#1: Protein | Mass: 45445.121 Da / Num. of mol.: 1 / Fragment: unp residues 57-453 Source method: isolated from a genetically manipulated source 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 | ChemComp-NI / |
#3: Chemical | ChemComp-3J9 / ( |
#4: 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: 2.15 Å3/Da / Density % sol: 42.87 % |
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Crystal grow | Temperature: 290 K / Method: vapor diffusion, hanging drop / pH: 4.5 Details: 16% PEG3K, 0.1M NaAcetate, 5% DMSO, pH 4.5, VAPOR DIFFUSION, HANGING DROP, temperature 290K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU FR-E+ SUPERBRIGHT / Wavelength: 1.5418 Å |
Detector | Type: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: Mar 14, 2011 / Details: Confocal mirrors |
Radiation | Monochromator: Confocal mirrors / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 1.8→30 Å / Num. all: 36683 / Num. obs: 35619 / % possible obs: 97.1 % / Observed criterion σ(I): 0 / Redundancy: 6.8 % / Rmerge(I) obs: 0.06 / Rsym value: 0.055 / Net I/σ(I): 14.4 |
Reflection shell | Resolution: 1.8→1.9 Å / Redundancy: 7 % / Rmerge(I) obs: 0.122 / Mean I/σ(I) obs: 7 / Num. unique all: 5270 / Rsym value: 0.122 / % possible all: 81.4 |
-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: pdb entry 4N00 Resolution: 1.8→28.07 Å / Cor.coef. Fo:Fc: 0.948 / Cor.coef. Fo:Fc free: 0.921 / SU B: 2.494 / SU ML: 0.08 / Cross valid method: THROUGHOUT / ESU R: 0.143 / ESU R Free: 0.136 / 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: BABINET MODEL WITH MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 29.309 Å2
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Refinement step | Cycle: LAST / Resolution: 1.8→28.07 Å
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Refine LS restraints |
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