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Yorodumi- PDB-5hu1: BACE1 in complex with (R)-N-(3-(3-amino-2,5-dimethyl-1,1-dioxido-... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5hu1 | ||||||
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Title | BACE1 in complex with (R)-N-(3-(3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-5-fluoropicolinamide | ||||||
Components | Beta-secretase 1 | ||||||
Keywords | HYDROLASE/HYDROLASE INHIBITOR / ALZHEIMER'S / ASPARTYL PROTEASE / HYDROLASE / 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 / prepulse inhibition / amyloid-beta metabolic process ...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 / prepulse inhibition / amyloid-beta metabolic process / detection of mechanical stimulus involved in sensory perception of pain / cellular response to copper ion / hippocampal mossy fiber to CA3 synapse / presynaptic modulation of chemical synaptic transmission / 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 / amyloid-beta binding / peptidase activity / endopeptidase activity / amyloid fibril formation / lysosome / aspartic-type endopeptidase activity / early endosome / endosome membrane / endosome / membrane raft / Amyloid fiber formation / axon / endoplasmic reticulum lumen / 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 / SYNCHROTRON / Resolution: 1.5 Å | ||||||
Authors | Orth, P. | ||||||
Citation | Journal: J. Med. Chem. / Year: 2016 Title: Discovery of the 3-Imino-1,2,4-thiadiazinane 1,1-Dioxide Derivative Verubecestat (MK-8931)-A beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor for the Treatment of Alzheimer's Disease. Authors: Scott, J.D. / Li, S.W. / Brunskill, A.P. / Chen, X. / Cox, K. / Cumming, J.N. / Forman, M. / Gilbert, E.J. / Hodgson, R.A. / Hyde, L.A. / Jiang, Q. / Iserloh, U. / Kazakevich, I. / Kuvelkar, ...Authors: Scott, J.D. / Li, S.W. / Brunskill, A.P. / Chen, X. / Cox, K. / Cumming, J.N. / Forman, M. / Gilbert, E.J. / Hodgson, R.A. / Hyde, L.A. / Jiang, Q. / Iserloh, U. / Kazakevich, I. / Kuvelkar, R. / Mei, H. / Meredith, J. / Misiaszek, J. / Orth, P. / Rossiter, L.M. / Slater, M. / Stone, J. / Strickland, C.O. / Voigt, J.H. / Wang, G. / Wang, H. / Wu, Y. / Greenlee, W.J. / Parker, E.M. / Kennedy, M.E. / Stamford, A.W. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5hu1.cif.gz | 181.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5hu1.ent.gz | 146.8 KB | Display | PDB format |
PDBx/mmJSON format | 5hu1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/hu/5hu1 ftp://data.pdbj.org/pub/pdb/validation_reports/hu/5hu1 | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 45979.578 Da / Num. of mol.: 2 / Fragment: UNP residues 43-454 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 | #3: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.99 Å3/Da / Density % sol: 58.89 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / Details: 15% PEG 3350, 200MM NA/K TARTRATE, 100MM HEPES PH7 |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Mar 20, 2015 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.5→50 Å / Num. obs: 163466 / % possible obs: 99.7 % / Redundancy: 5 % / Rmerge(I) obs: 0.072 / Χ2: 1.071 / Net I/av σ(I): 19.187 / Net I/σ(I): 6.2 / Num. measured all: 820641 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Processing
Software |
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Refinement | Resolution: 1.5→45.33 Å / Cor.coef. Fo:Fc: 0.9599 / Cor.coef. Fo:Fc free: 0.9566 / Occupancy max: 1 / Occupancy min: 0.5 / Cross valid method: THROUGHOUT / σ(F): 0
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Displacement parameters | Biso max: 114.9 Å2 / Biso mean: 21.235 Å2 / Biso min: 8.56 Å2
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Refine analyze | Luzzati coordinate error obs: 0.196 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.5→45.33 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.5→1.54 Å / Total num. of bins used: 20
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