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Yorodumi- PDB-4dh6: Structure of Bace-1 (Beta-Secretase) in Complex with (2R)-N-((2S,... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4dh6 | ||||||
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Title | Structure of Bace-1 (Beta-Secretase) in Complex with (2R)-N-((2S,3R)-1-(benzo[d][1,3]dioxol-5-yl)-3-hydroxy-4-((S)-6'-neopentyl-3',4'-dihydrospiro[cyclobutane-1,2'-pyrano[2,3-b]pyridine]-4'-ylamino)butan-2-yl)-2-methoxypropanamide | ||||||
Components | Beta-secretase 1 | ||||||
Keywords | HYDROLASE/HYDROLASE INHIBITOR / Bace-1 / Beta-Secretase / 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 / prepulse inhibition / detection of mechanical stimulus involved in sensory perception of pain ...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 / detection of mechanical stimulus involved in sensory perception of pain / amyloid-beta metabolic process / 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 / MOLECULAR REPLACEMENT / Resolution: 2.5 Å | ||||||
Authors | Sickmier, E.A. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2012 Title: Design and preparation of a potent series of hydroxyethylamine containing beta-secretase inhibitors that demonstrate robust reduction of central beta-amyloid. Authors: Weiss, M.M. / Williamson, T. / Babu-Khan, S. / Bartberger, M.D. / Brown, J. / Chen, K. / Cheng, Y. / Citron, M. / Croghan, M.D. / Dineen, T.A. / Esmay, J. / Graceffa, R.F. / Harried, S.S. / ...Authors: Weiss, M.M. / Williamson, T. / Babu-Khan, S. / Bartberger, M.D. / Brown, J. / Chen, K. / Cheng, Y. / Citron, M. / Croghan, M.D. / Dineen, T.A. / Esmay, J. / Graceffa, R.F. / Harried, S.S. / Hickman, D. / Hitchcock, S.A. / Horne, D.B. / Huang, H. / Imbeah-Ampiah, R. / Judd, T. / Kaller, M.R. / Kreiman, C.R. / La, D.S. / Li, V. / Lopez, P. / Louie, S. / Monenschein, H. / Nguyen, T.T. / Pennington, L.D. / Rattan, C. / San Miguel, T. / Sickmier, E.A. / Wahl, R.C. / Wen, P.H. / Wood, S. / Xue, Q. / Yang, B.H. / Patel, V.F. / Zhong, W. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4dh6.cif.gz | 86.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4dh6.ent.gz | 69.2 KB | Display | PDB format |
PDBx/mmJSON format | 4dh6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dh/4dh6 ftp://data.pdbj.org/pub/pdb/validation_reports/dh/4dh6 | HTTPS FTP |
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-Related structure data
Similar structure data |
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-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 45822.445 Da / Num. of mol.: 1 / Fragment: UNP residues 43-453 / Mutation: R-5K, R-4K 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 | #4: Chemical | ChemComp-0KN / ( | #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: 2.86 Å3/Da / Density % sol: 56.99 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 6.6 Details: 20 % (w/v) PEG 5000 monomethylethyl ether (MME), 200 mM sodium citrate (pH 6.6) and 200 mM sodium iodide, VAPOR DIFFUSION, HANGING DROP, temperature 298K |
-Data collection
Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1.000036 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Detector | Date: May 26, 2009 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1.000036 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.5→30 Å / Num. all: 19204 / Num. obs: 19204 / % possible obs: 99.2 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 11.4 % / Rmerge(I) obs: 0.075 / Χ2: 1.033 / Net I/σ(I): 11.4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.5→20 Å / Cor.coef. Fo:Fc: 0.925 / Cor.coef. Fo:Fc free: 0.895 / WRfactor Rfree: 0.2634 / WRfactor Rwork: 0.2185 / Occupancy max: 1 / Occupancy min: 0.25 / FOM work R set: 0.7987 / SU B: 8.678 / SU ML: 0.195 / SU R Cruickshank DPI: 0.4618 / SU Rfree: 0.2966 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.462 / ESU R Free: 0.297 / 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: MASK | |||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 440 Å2 / Biso mean: 40.5371 Å2 / Biso min: 14.55 Å2
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Refinement step | Cycle: LAST / Resolution: 2.5→20 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.5→2.564 Å / Total num. of bins used: 20
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