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Yorodumi- PDB-6jsn: Crystal Structure of BACE1 in complex with N-{3-[(5R)-3-amino-5-m... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6jsn | ||||||
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Title | Crystal Structure of BACE1 in complex with N-{3-[(5R)-3-amino-5-methyl-9,9-dioxo-2,9lambda6-dithia-4-azaspiro[5.5]undec-3-en-5-yl]-4-fluorophenyl}-5-(fluoromethoxy)pyrazine-2-carboxamide | ||||||
Components | Beta-secretase 1 | ||||||
Keywords | HYDROLASE / GS-hBACE1(43-454) | ||||||
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 / early endosome / lysosome / 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: 2.6 Å | ||||||
Authors | Fujimoto, K. / Matsuoka, E. / Asada, N. / Tadano, G. / Yamamoto, T. / Nakahara, K. / Fuchino, K. / Ito, H. / Kanegawa, N. / Moechars, D. ...Fujimoto, K. / Matsuoka, E. / Asada, N. / Tadano, G. / Yamamoto, T. / Nakahara, K. / Fuchino, K. / Ito, H. / Kanegawa, N. / Moechars, D. / Gijsen, H.J.M. / Kusakabe, K.I. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2019 Title: Structure-Based Design of Selective beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitors: Targeting the Flap to Gain Selectivity over BACE2. Authors: Fujimoto, K. / Matsuoka, E. / Asada, N. / Tadano, G. / Yamamoto, T. / Nakahara, K. / Fuchino, K. / Ito, H. / Kanegawa, N. / Moechars, D. / Gijsen, H.J.M. / Kusakabe, K.I. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6jsn.cif.gz | 93.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6jsn.ent.gz | 68.2 KB | Display | PDB format |
PDBx/mmJSON format | 6jsn.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6jsn_validation.pdf.gz | 719.2 KB | Display | wwPDB validaton report |
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Full document | 6jsn_full_validation.pdf.gz | 724.1 KB | Display | |
Data in XML | 6jsn_validation.xml.gz | 17 KB | Display | |
Data in CIF | 6jsn_validation.cif.gz | 23.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/js/6jsn ftp://data.pdbj.org/pub/pdb/validation_reports/js/6jsn | HTTPS FTP |
-Related structure data
Related structure data | 6jseC 6jsfC 6jsgC 6jszC 1w50S 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: 46393.043 Da / Num. of mol.: 1 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-IOD / #3: Chemical | ChemComp-GOL / | #4: Chemical | ChemComp-C7O / | #5: 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: 3 Å3/Da / Density % sol: 59.06 % |
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Crystal grow | Temperature: 293.15 K / Method: vapor diffusion, sitting drop / pH: 6.5 Details: 0.2 M sodium citrate, 0.2 M ammonium iodide, 19%(w/v) polyethylene glycol 5000 monomethyl ether, pH 6.5 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.54178 Å |
Detector | Type: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: Jul 22, 2016 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54178 Å / Relative weight: 1 |
Reflection | Resolution: 2.6→50 Å / Num. obs: 16705 / % possible obs: 99.7 % / Redundancy: 7.3 % / Rmerge(I) obs: 0.18 / Net I/σ(I): 22.3 |
Reflection shell | Resolution: 2.6→2.64 Å / Rmerge(I) obs: 0.553 / Num. unique obs: 799 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1W50 Resolution: 2.6→20 Å / Cor.coef. Fo:Fc: 0.939 / Cor.coef. Fo:Fc free: 0.898 / SU B: 10.417 / SU ML: 0.219 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.569 / ESU R Free: 0.315 Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT U VALUES : REFINED INDIVIDUALLY
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 120.34 Å2 / Biso mean: 44.745 Å2 / Biso min: 22.42 Å2
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Refinement step | Cycle: final / Resolution: 2.6→20 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.6→2.666 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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