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Yorodumi- PDB-3qi1: Design and synthesis of hydroxyethylamine (hea) BACE-1 inhibitors... -
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-Basic information
Entry | Database: PDB / ID: 3qi1 | ||||||
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Title | Design and synthesis of hydroxyethylamine (hea) BACE-1 inhibitors: prime side chromane-containing inhibitors | ||||||
Components | Beta-secretase 1 | ||||||
Keywords | HYDROLASE/HYDROLASE INHIBITOR / Aspartate 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 / prepulse inhibition / amyloid-beta metabolic process ...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 / amyloid-beta metabolic process / detection of mechanical stimulus involved in sensory perception of pain / 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 / MOLECULAR REPLACEMENT / Resolution: 2.3 Å | ||||||
Authors | Yao, N. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2013 Title: Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: prime side chromane-containing inhibitors. Authors: Ng, R.A. / Sun, M. / Bowers, S. / Hom, R.K. / Probst, G.D. / John, V. / Fang, L.Y. / Maillard, M. / Gailunas, A. / Brogley, L. / Neitz, R.J. / Tung, J.S. / Pleiss, M.A. / Konradi, A.W. / ...Authors: Ng, R.A. / Sun, M. / Bowers, S. / Hom, R.K. / Probst, G.D. / John, V. / Fang, L.Y. / Maillard, M. / Gailunas, A. / Brogley, L. / Neitz, R.J. / Tung, J.S. / Pleiss, M.A. / Konradi, A.W. / Sham, H.L. / Dappen, M.S. / Adler, M. / Yao, N. / Zmolek, W. / Nakamura, D. / Quinn, K.P. / Sauer, J.M. / Bova, M.P. / Ruslim, L. / Artis, D.R. / Yednock, T.A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3qi1.cif.gz | 90.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3qi1.ent.gz | 72.1 KB | Display | PDB format |
PDBx/mmJSON format | 3qi1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qi/3qi1 ftp://data.pdbj.org/pub/pdb/validation_reports/qi/3qi1 | HTTPS FTP |
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-Related structure data
Similar structure data |
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-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 45394.871 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: BACE, BACE1, KIAA1149 / Production host: Escherichia coli (E. coli) / References: UniProt: P56817, memapsin 2 |
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#2: Chemical | ChemComp-C6A / |
#3: 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: 2.41 Å3/Da / Density % sol: 48.96 % |
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Crystal grow | Temperature: 295 K / pH: 4.6 Details: BACE PROTEIN AT 10MG/ML IN 100MM SODIUM BORATE BUFFER PH 8.5. 1MM COMPOUND ADDED TO PROTEIN AND INCUBATED AT 4 C FOR 3 HOURS. HANGING DROP PLATES SET UP WITH RESERVOIR SOLUTION CONTAINING 4% ...Details: BACE PROTEIN AT 10MG/ML IN 100MM SODIUM BORATE BUFFER PH 8.5. 1MM COMPOUND ADDED TO PROTEIN AND INCUBATED AT 4 C FOR 3 HOURS. HANGING DROP PLATES SET UP WITH RESERVOIR SOLUTION CONTAINING 4% PEG 8000, 100MM SODIUM ACETATE PH 4.6 THE DROPS WERE MIXED WITH 1:1 (V/V) RATIO OF PROTEIN/COMPOUND TO RESERVOIR AND INCUBATED AT ROOM TEMPERATURE FOR 2 WEEKS. VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 295K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU MICROMAX-007 / Wavelength: 1.5418 |
Detector | Type: RIGAKU RAXIS HTC / Detector: IMAGE PLATE / Date: Jul 30, 2010 / Details: MIRRORS |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 2.3→25.69 Å / Num. obs: 19292 / % possible obs: 96.2 % / Observed criterion σ(I): 1 / Redundancy: 3.89 % / Rmerge(I) obs: 0.086 / Net I/σ(I): 9.2 |
Reflection shell | Resolution: 2.3→2.38 Å / Redundancy: 3.86 % / Rmerge(I) obs: 0.406 / Mean I/σ(I) obs: 2.3 / % possible all: 99.8 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.3→25.69 Å / Cor.coef. Fo:Fc: 0.946 / Cor.coef. Fo:Fc free: 0.908 / SU B: 7 / SU ML: 0.17 / Cross valid method: THROUGHOUT / ESU R: 0.368 / ESU R Free: 0.269 / 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: 29.646 Å2
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Refinement step | Cycle: LAST / Resolution: 2.3→25.69 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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