[English] 日本語
Yorodumi- PDB-4n00: Discovery of 7-THP chromans: BACE1 inhibitors that reduce A-beta ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4n00 | ||||||
---|---|---|---|---|---|---|---|
Title | Discovery of 7-THP chromans: BACE1 inhibitors that reduce A-beta in the CNS | ||||||
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 / 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: 1.8 Å | ||||||
Authors | Vigers, G.P.A. / Smith, D. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2014 Title: Discovery of 7-tetrahydropyran-2-yl chromans: beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors that reduce amyloid beta-protein (A beta ) in the central nervous system. Authors: Thomas, A.A. / Hunt, K.W. / Volgraf, M. / Watts, R.J. / Liu, X. / Vigers, G. / Smith, D. / Sammond, D. / Tang, T.P. / Rhodes, S.P. / Metcalf, A.T. / Brown, K.D. / Otten, J.N. / Burkard, M. / ...Authors: Thomas, A.A. / Hunt, K.W. / Volgraf, M. / Watts, R.J. / Liu, X. / Vigers, G. / Smith, D. / Sammond, D. / Tang, T.P. / Rhodes, S.P. / Metcalf, A.T. / Brown, K.D. / Otten, J.N. / Burkard, M. / Cox, A.A. / Do, M.K. / Dutcher, D. / Rana, S. / DeLisle, R.K. / Regal, K. / Wright, A.D. / Groneberg, R. / Scearce-Levie, K. / Siu, M. / Purkey, H.E. / Lyssikatos, J.P. / Gunawardana, I.W. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 4n00.cif.gz | 97 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb4n00.ent.gz | 71.6 KB | Display | PDB format |
PDBx/mmJSON format | 4n00.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/n0/4n00 ftp://data.pdbj.org/pub/pdb/validation_reports/n0/4n00 | HTTPS FTP |
---|
-Related structure data
Related structure data | 4jp9S S: Starting model for refinement |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
| ||||||||
Components on special symmetry positions |
|
-Components
#1: Protein | Mass: 45445.121 Da / Num. of mol.: 1 / Fragment: Bace1 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 |
---|---|
#2: Chemical | ChemComp-NI / |
#3: Chemical | ChemComp-2EX / ( |
#4: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.15 Å3/Da / Density % sol: 42.85 % |
---|---|
Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 4.5 Details: 16% PEG3K, 0.1M NaAcetate, pH 4.5, VAPOR DIFFUSION, HANGING DROP, temperature 293K |
-Data collection
Diffraction | Mean temperature: 100 K |
---|---|
Diffraction source | Source: ROTATING ANODE / Type: RIGAKU FR-E SUPERBRIGHT / Wavelength: 1.5418 Å |
Detector | Type: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: Oct 22, 2010 / 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: 36623 / Num. obs: 35504 / % possible obs: 96.9 % / Observed criterion σ(I): 3.5 / Redundancy: 6.82 % / Rmerge(I) obs: 0.094 / Rsym value: 0.085 / Net I/σ(I): 13.2 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: pdb entry 4JP9 Resolution: 1.8→28.14 Å / Cor.coef. Fo:Fc: 0.952 / Cor.coef. Fo:Fc free: 0.935 / SU B: 2.659 / SU ML: 0.084 / Cross valid method: THROUGHOUT / ESU R: 0.146 / ESU R Free: 0.137 / Stereochemistry target values: MAXIMUM LIKELIHOOD
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 26.287 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.8→28.14 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
|