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Yorodumi- PDB-4jpc: Spirocyclic Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4jpc | ||||||
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Title | Spirocyclic 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: 2013 Title: Spirocyclic beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors: from hit to lowering of cerebrospinal fluid (CSF) amyloid beta in a higher species. Authors: Hunt, K.W. / Cook, A.W. / Watts, R.J. / Clark, C.T. / Vigers, G. / Smith, D. / Metcalf, A.T. / Gunawardana, I.W. / Burkard, M. / Cox, A.A. / Geck Do, M.K. / Dutcher, D. / Thomas, A.A. / ...Authors: Hunt, K.W. / Cook, A.W. / Watts, R.J. / Clark, C.T. / Vigers, G. / Smith, D. / Metcalf, A.T. / Gunawardana, I.W. / Burkard, M. / Cox, A.A. / Geck Do, M.K. / Dutcher, D. / Thomas, A.A. / Rana, S. / Kallan, N.C. / DeLisle, R.K. / Rizzi, J.P. / Regal, K. / Sammond, D. / Groneberg, R. / Siu, M. / Purkey, H. / Lyssikatos, J.P. / Marlow, A. / Liu, X. / Tang, T.P. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4jpc.cif.gz | 102 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4jpc.ent.gz | 75.4 KB | Display | PDB format |
PDBx/mmJSON format | 4jpc.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4jpc_validation.pdf.gz | 766 KB | Display | wwPDB validaton report |
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Full document | 4jpc_full_validation.pdf.gz | 770.4 KB | Display | |
Data in XML | 4jpc_validation.xml.gz | 19.5 KB | Display | |
Data in CIF | 4jpc_validation.cif.gz | 29 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jp/4jpc ftp://data.pdbj.org/pub/pdb/validation_reports/jp/4jpc | HTTPS FTP |
-Related structure data
Related structure data | 4jooC 4jp9C 4jpeC 2oahS C: citing same article (ref.) S: Starting model for refinement |
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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: 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 |
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#2: Chemical | ChemComp-NI / |
#3: Chemical | ChemComp-1M6 / |
#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: 42.79 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 4.5 Details: 16% PEG3K, 0.1M Na Acetate, 5% DMSO , pH 4.5, VAPOR DIFFUSION, HANGING DROP, temperature 293K |
-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: Jul 15, 2009 / Details: Osmic mirrors |
Radiation | Monochromator: Osmic 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: 36632 / Num. obs: 35067 / % possible obs: 95.7 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 2 / Redundancy: 6.64 % / Rmerge(I) obs: 0.062 / Rsym value: 0.056 / Net I/σ(I): 16.78 |
Reflection shell | Resolution: 1.8→1.9 Å / Redundancy: 4.11 % / Rmerge(I) obs: 0.144 / Mean I/σ(I) obs: 6 / Num. unique all: 5272 / Rsym value: 0.144 / % possible all: 73.5 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2OAH Resolution: 1.8→17.08 Å / Cor.coef. Fo:Fc: 0.951 / Cor.coef. Fo:Fc free: 0.94 / SU B: 2.489 / SU ML: 0.078 / Cross valid method: THROUGHOUT / ESU R: 0.147 / ESU R Free: 0.127 / 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: 22.018 Å2
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Refinement step | Cycle: LAST / Resolution: 1.8→17.08 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.8→1.846 Å / Total num. of bins used: 20
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