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Yorodumi- PDB-4d8c: Crystal Structure of Human Beta Secretase in Complex with NVP-BXD... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4d8c | ||||||
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Title | Crystal Structure of Human Beta Secretase in Complex with NVP-BXD552, derived from a co-crystallization experiment | ||||||
Components | Beta-secretase 1 | ||||||
Keywords | Hydrolase/Hydrolase inhibitor / Beta-Secretase / Memapsin2 / Bace1 / Aspartic Proteinase / Alzheimer's disease / Enzyme inhibitor complex / Structure-based drug design / Hydrolase / 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: 2.07 Å | ||||||
Authors | Rondeau, J.M. / Bourgier, E. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2012 Title: Discovery of cyclic sulfone hydroxyethylamines as potent and selective beta-site APP-cleaving enzyme 1 (BACE1) inhibitors: structure based design and in vivo reduction of amyloid beta-peptides Authors: Rueeger, H. / Lueoend, R. / Rogel, O. / Rondeau, J.M. / Mobitz, H. / Machauer, R. / Jacobson, L. / Staufenbiel, M. / Desrayaud, S. / Neumann, U. #1: Journal: Bioorg.Med.Chem.Lett. / Year: 2011 Title: Structure-Based Design, synthesis and SAR of cyclic hydroxyethylamine (HEA) BACE-1 inhibitors Authors: Rueeger, H. / Rondeau, J.M. / McCarthy, C. / Moebitz, H. / Tintelnot-Blomley, M. / Neumann, U. / Desrayaud, S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4d8c.cif.gz | 247.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4d8c.ent.gz | 204.7 KB | Display | PDB format |
PDBx/mmJSON format | 4d8c.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/d8/4d8c ftp://data.pdbj.org/pub/pdb/validation_reports/d8/4d8c | HTTPS FTP |
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-Related structure data
Related structure data | 3veuC 3vf3C 3vg1C 4d83C 4d85C 4d88C 4d89C 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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2 |
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3 |
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Unit cell |
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-Components
#1: Protein | Mass: 44777.336 Da / Num. of mol.: 3 / Fragment: Catalytic domain (unp residues 48-447) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BACE, BACE1, KIAA1149 / Plasmid: pET24 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P56817, memapsin 2 #2: Chemical | #3: Chemical | #4: 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: 3.08 Å3/Da / Density % sol: 60.1 % |
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Crystal grow | Temperature: 292 K / Method: vapor diffusion, hanging drop / pH: 5.5 Details: 1.0M ammonium sulfate in water, pH 5.5, vapor diffusion, hanging drop, temperature 292K |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1.00161 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Jan 31, 2008 / Details: mirrors | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Monochromator: SAGITALLY FOCUSED Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1.00161 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.07→71.05 Å / Num. all: 99152 / Num. obs: 99152 / % possible obs: 99.8 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 4.6 % / Biso Wilson estimate: 40.235 Å2 / Rmerge(I) obs: 0.058 / Net I/σ(I): 14.41 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS / Resolution: 2.07→70.95 Å / Rfactor Rfree error: 0.002 / Occupancy max: 1 / Occupancy min: 1 / FOM work R set: 0.8696 / Data cutoff high absF: 2418357 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
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Solvent computation | Solvent model: FLAT MODEL / Bsol: 54.3088 Å2 / ksol: 0.3707 e/Å3 | ||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 111.28 Å2 / Biso mean: 40.5968 Å2 / Biso min: 19.23 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 2.07→70.95 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.07→2.2 Å / Rfactor Rfree error: 0.006 / Total num. of bins used: 6
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Xplor file |
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