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Yorodumi- PDB-4i0e: Design and Synthesis of Thiophene Dihydroisoquinolins as Novel BA... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4i0e | ||||||
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Title | Design and Synthesis of Thiophene Dihydroisoquinolins as Novel BACE-1 Inhibitors | ||||||
Components | Beta-secretase 1 | ||||||
Keywords | hydrolase/hydrolase inhibitor / BACE / aspartic protease / hydrolysis / 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 / MOLECULAR REPLACEMENT / Resolution: 1.7 Å | ||||||
Authors | Yao, N. / Brecht, E. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2013 Title: Design and synthesis of thiophene dihydroisoquinolines as novel BACE1 inhibitors. Authors: Xu, Y.Z. / Yuan, S. / Bowers, S. / Hom, R.K. / Chan, W. / Sham, H.L. / Zhu, Y.L. / Beroza, P. / Pan, H. / Brecht, E. / Yao, N. / Lougheed, J. / Yan, J. / Tam, D. / Ren, Z. / Ruslim, L. / Bova, M.P. / Artis, D.R. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4i0e.cif.gz | 94.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4i0e.ent.gz | 75.4 KB | Display | PDB format |
PDBx/mmJSON format | 4i0e.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/i0/4i0e ftp://data.pdbj.org/pub/pdb/validation_reports/i0/4i0e | 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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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 / References: UniProt: P56817, memapsin 2 | ||||
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#2: Chemical | #3: Chemical | ChemComp-1B8 / | #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: 2.14 Å3/Da / Density % sol: 42.52 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 5.3 Details: BACE was concentrated to 10mg/ml in 100 mM borate pH 8.5, 9% PEG 8000, 100mM sodium acetate and 10mM ZnCl2, VAPOR DIFFUSION, SITTING DROP, temperature 277K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.5418 Å |
Detector | Type: RIGAKU SATURN 944+ / Detector: CCD / Date: Jan 1, 2011 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 1.7→60 Å / Num. all: 39688 / Num. obs: 41475 / % possible obs: 92 % / Observed criterion σ(F): 1 / Observed criterion σ(I): 1 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.7→60 Å / Cor.coef. Fo:Fc: 0.959 / Cor.coef. Fo:Fc free: 0.93 / SU B: 4.718 / SU ML: 0.145 / Cross valid method: THROUGHOUT / ESU R: 0.145 / ESU R Free: 0.153 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 36.853 Å2
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Refinement step | Cycle: LAST / Resolution: 1.7→60 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.63→1.672 Å / Total num. of bins used: 20
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