+Open data
-Basic information
Entry | Database: PDB / ID: 4dpf | ||||||
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Title | BACE-1 in complex with a HEA-macrocyclic type inhibitor | ||||||
Components | Beta-secretase 1 | ||||||
Keywords | Hydrolase/Hydrolase inhibitor / BACE1 / ASP2 / BACE / macrocycle / 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 / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.8 Å | ||||||
Authors | Lindberg, J. / Borkakoti, N. / Derbyshire, D. | ||||||
Citation | Journal: Bioorg.Med.Chem. / Year: 2012 Title: Highly potent macrocyclic BACE-1 inhibitors incorporating a hydroxyethylamine core: design, synthesis and X-ray crystal structures of enzyme inhibitor complexes. Authors: Sandgren, V. / Agback, T. / Johansson, P.O. / Lindberg, J. / Kvarnstrom, I. / Samuelsson, B. / Belda, O. / Dahlgren, A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4dpf.cif.gz | 163.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4dpf.ent.gz | 133.3 KB | Display | PDB format |
PDBx/mmJSON format | 4dpf.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dp/4dpf ftp://data.pdbj.org/pub/pdb/validation_reports/dp/4dpf | 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: 43601.195 Da / Num. of mol.: 1 / Fragment: unp residues 57-446 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BACE1, BACE, KIAA1149 / Plasmid: pET21 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P56817, memapsin 2 |
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#2: Chemical | ChemComp-0LG / |
#3: 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: 2.18 Å3/Da / Density % sol: 43.63 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion / pH: 4.5 Details: 18% PEG 1000, 0.1 Na-Acetate pH4.5, 5% Glycerol, vapor diffusion, temperature 291K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID23-2 / Wavelength: 0.976 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Jun 29, 2011 / Details: Mirrors |
Radiation | Monochromator: Graphite / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.976 Å / Relative weight: 1 |
Reflection | Resolution: 1.8→51.94 Å / Num. all: 36162 / Num. obs: 35772 / % possible obs: 98.9 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2 / Rmerge(I) obs: 0.077 |
Reflection shell | Resolution: 1.8→1.9 Å / Redundancy: 2.2 % / Rmerge(I) obs: 0.325 / Mean I/σ(I) obs: 2.3 / Num. unique all: 4817 / % possible all: 93.2 |
-Phasing
Phasing | Method: molecular replacement | |||||||||
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Phasing MR | Rfactor: 39.71 / Model details: Phaser MODE: MR_AUTO
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.8→43.39 Å / Cor.coef. Fo:Fc: 0.949 / Cor.coef. Fo:Fc free: 0.933 / WRfactor Rfree: 0.2412 / WRfactor Rwork: 0.1917 / Occupancy max: 1 / Occupancy min: 0.3 / FOM work R set: 0.8418 / SU B: 6.981 / SU ML: 0.098 / SU R Cruickshank DPI: 0.1411 / SU Rfree: 0.1374 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.141 / ESU R Free: 0.137 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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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: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 58.31 Å2 / Biso mean: 20.5565 Å2 / Biso min: 5.1 Å2
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Refinement step | Cycle: LAST / Resolution: 1.8→43.39 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.8→1.847 Å / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Origin x: -2.375 Å / Origin y: 1.4164 Å / Origin z: -14.971 Å
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