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Yorodumi- PDB-7d2x: Crystal Structure of BACE1 in complex with N-{3-[(4R)-2-amino-4-(... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7d2x | ||||||
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Title | Crystal Structure of BACE1 in complex with N-{3-[(4R)-2-amino-4-(prop-1-yn-1-yl)-5,6-dihydro-4H-1,3-oxazin-4-yl]-4-fluorophenyl}-5-cyanopyridine-2-carboxamide | ||||||
Components | Beta-secretase 1 | ||||||
Keywords | HYDROLASE / BACE1 | ||||||
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 / amyloid-beta metabolic process / cellular response to manganese ion / 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 / amyloid-beta metabolic process / cellular response to manganese ion / 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 / multivesicular body / hippocampal mossy fiber to CA3 synapse / response to lead ion / trans-Golgi network / recycling endosome / protein processing / cellular response to amyloid-beta / positive regulation of neuron apoptotic process / late endosome / synaptic vesicle / peptidase activity / amyloid-beta binding / endopeptidase activity / aspartic-type endopeptidase activity / amyloid fibril formation / endosome / endosome membrane / early endosome / lysosome / membrane raft / Amyloid fiber formation / endoplasmic reticulum lumen / axon / neuronal cell body / dendrite / enzyme binding / cell surface / Golgi apparatus / proteolysis / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.45 Å | ||||||
Authors | Fujimoto, K. / Yoshida, S. / Tadano, G. / Asada, N. / Fuchino, K. / Suzuki, S. / Matsuoka, E. / Yamamoto, T. / Yamamoto, S. / Ando, S. ...Fujimoto, K. / Yoshida, S. / Tadano, G. / Asada, N. / Fuchino, K. / Suzuki, S. / Matsuoka, E. / Yamamoto, T. / Yamamoto, S. / Ando, S. / Kanegawa, N. / Tonomura, Y. / Ito, H. / Moechars, D. / Rombouts, F.J.R. / Gijsen, H.J.M. / Kusakabe, K.I. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2021 Title: Structure-Based Approaches to Improving Selectivity through Utilizing Explicit Water Molecules: Discovery of Selective beta-Secretase (BACE1) Inhibitors over BACE2. Authors: Fujimoto, K. / Yoshida, S. / Tadano, G. / Asada, N. / Fuchino, K. / Suzuki, S. / Matsuoka, E. / Yamamoto, T. / Yamamoto, S. / Ando, S. / Kanegawa, N. / Tonomura, Y. / Ito, H. / Moechars, D. ...Authors: Fujimoto, K. / Yoshida, S. / Tadano, G. / Asada, N. / Fuchino, K. / Suzuki, S. / Matsuoka, E. / Yamamoto, T. / Yamamoto, S. / Ando, S. / Kanegawa, N. / Tonomura, Y. / Ito, H. / Moechars, D. / Rombouts, F.J.R. / 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 | 7d2x.cif.gz | 95.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7d2x.ent.gz | 69 KB | Display | PDB format |
PDBx/mmJSON format | 7d2x.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/d2/7d2x ftp://data.pdbj.org/pub/pdb/validation_reports/d2/7d2x | HTTPS FTP |
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-Related structure data
Related structure data | 7d2vC 7d5aC 7d5bC 7d5uC 1w50S S: Starting model for refinement 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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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 | #3: Chemical | #4: Chemical | ChemComp-GTU / | #5: Water | ChemComp-HOH / | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.73 Å3/Da / Density % sol: 54.87 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5 Details: 0.2 M sodium citrate tribasic pH 6.5, 0.2 M ammonium iodide, 19.6% w/v PEG 5000MME |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU FR-E+ SUPERBRIGHT / Wavelength: 1.54178 Å |
Detector | Type: RIGAKU SATURN 944 / Detector: CCD / Date: Dec 2, 2014 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54178 Å / Relative weight: 1 |
Reflection | Resolution: 2.45→50 Å / Num. obs: 19602 / % possible obs: 99 % / Redundancy: 6.7 % / Rmerge(I) obs: 0.012 / Net I/σ(I): 10.9 |
Reflection shell | Resolution: 2.45→2.58 Å / Rmerge(I) obs: 0.5 / Num. unique obs: 19602 |
-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 Starting model: 1W50 Resolution: 2.45→20 Å / Cor.coef. Fo:Fc: 0.945 / Cor.coef. Fo:Fc free: 0.914 / SU B: 6.647 / SU ML: 0.154 / SU R Cruickshank DPI: 0.333 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.333 / ESU R Free: 0.235 / Stereochemistry target values: MAXIMUM LIKELIHOOD 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 / Solvent model: BABINET MODEL WITH MASK | |||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 82.57 Å2 / Biso mean: 39.417 Å2 / Biso min: 23.74 Å2
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Refinement step | Cycle: final / Resolution: 2.45→20 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.45→2.513 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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