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Yorodumi- PDB-3vv7: Crystal Structure of beta secetase in complex with 2-amino-6-((1S... -
+Open data
-Basic information
Entry | Database: PDB / ID: 3vv7 | ||||||
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Title | Crystal Structure of beta secetase in complex with 2-amino-6-((1S,2R)-2-(3'-methoxybiphenyl-3-yl)cyclopropyl)-3-methylpyrimidin-4(3H)-one | ||||||
Components | Beta-secretase 1 | ||||||
Keywords | HYDROLASE/HYDROLASE INHIBITOR / ASPARTYL PROTEASE / BASE / BETA-SECRETASE / 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 / molecular replacement / Resolution: 2.1 Å | ||||||
Authors | Yonezawa, S. / Yamamoto, T. / Yamakawa, H. / Muto, C. / Hosono, M. / Hattori, K. / Higashino, K. / Sakagami, M. / Togame, H. / Tanaka, Y. ...Yonezawa, S. / Yamamoto, T. / Yamakawa, H. / Muto, C. / Hosono, M. / Hattori, K. / Higashino, K. / Sakagami, M. / Togame, H. / Tanaka, Y. / Nakano, T. / Takemoto, H. / Arisawa, M. / Shuto, S. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2012 Title: Conformational restriction approach to beta-secretase (BACE1) inhibitors: effect of a cyclopropane ring to induce an alternative binding mode. Authors: Yonezawa, S. / Yamamoto, T. / Yamakawa, H. / Muto, C. / Hosono, M. / Hattori, K. / Higashino, K. / Yutsudo, T. / Iwamoto, H. / Kondo, Y. / Sakagami, M. / Togame, H. / Tanaka, Y. / Nakano, T. ...Authors: Yonezawa, S. / Yamamoto, T. / Yamakawa, H. / Muto, C. / Hosono, M. / Hattori, K. / Higashino, K. / Yutsudo, T. / Iwamoto, H. / Kondo, Y. / Sakagami, M. / Togame, H. / Tanaka, Y. / Nakano, T. / Takemoto, H. / Arisawa, M. / Shuto, S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3vv7.cif.gz | 88.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3vv7.ent.gz | 69.2 KB | Display | PDB format |
PDBx/mmJSON format | 3vv7.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vv/3vv7 ftp://data.pdbj.org/pub/pdb/validation_reports/vv/3vv7 | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 46393.043 Da / Num. of mol.: 1 / Fragment: UNP RESIDUES 43-454 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BACE1 / Plasmid: pET28a / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P56817, memapsin 2 | ||||||
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#2: Chemical | ChemComp-IOD / #3: Chemical | #4: Chemical | ChemComp-0B1 / | #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: 2.83 Å3/Da / Density % sol: 56.48 % / Mosaicity: 0.484 ° |
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Crystal grow | Method: vapor diffusion, sitting drop / pH: 6.5 Details: 120mM sodium citrate, 200mM ammonium iodide, 30%(w/v) polyethylene glycol 5000 monomethyl ether, pH 6.5, VAPOR DIFFUSION, SITTING DROP |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: Apr 10, 2010 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.1→50 Å / Num. obs: 31474 / % possible obs: 98 % / Redundancy: 10.2 % / Rmerge(I) obs: 0.081 / Χ2: 1.093 / Net I/σ(I): 10.4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Phasing
Phasing | Method: molecular replacement | |||||||||
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Phasing MR |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.1→20 Å / Cor.coef. Fo:Fc: 0.924 / Cor.coef. Fo:Fc free: 0.907 / WRfactor Rfree: 0.2505 / WRfactor Rwork: 0.2179 / Occupancy max: 1 / Occupancy min: 1 / FOM work R set: 0.7991 / SU B: 4.997 / SU ML: 0.134 / SU R Cruickshank DPI: 0.2174 / SU Rfree: 0.1925 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.217 / ESU R Free: 0.193 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: U VALUES: REFINED INDIVIDUALLY
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: BABINET MODEL WITH MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 110.87 Å2 / Biso mean: 34.0888 Å2 / Biso min: 9.03 Å2
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Refinement step | Cycle: LAST / Resolution: 2.1→20 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.1→2.154 Å / Total num. of bins used: 20
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