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Yorodumi- PDB-5i3y: Crystal structure of BACE1 in complex with aminoquinoline inhibitor 9 -
+Open data
-Basic information
Entry | Database: PDB / ID: 5i3y | ||||||
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Title | Crystal structure of BACE1 in complex with aminoquinoline inhibitor 9 | ||||||
Components | Beta-secretase 1 | ||||||
Keywords | HYDROLASE/HYDROLASE Inhibitor / aspartic protease / amyloid precursor protein / Alzheimer's disease / 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 / protein serine/threonine kinase binding / 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 / aspartic-type endopeptidase activity / lysosome / 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 / Resolution: 2.15 Å | ||||||
Authors | Whittington, D.A. / Long, A.M. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2016 Title: Fragment-Linking Approach Using (19)F NMR Spectroscopy To Obtain Highly Potent and Selective Inhibitors of beta-Secretase. Authors: Jordan, J.B. / Whittington, D.A. / Bartberger, M.D. / Sickmier, E.A. / Chen, K. / Cheng, Y. / Judd, T. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5i3y.cif.gz | 173.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5i3y.ent.gz | 133.2 KB | Display | PDB format |
PDBx/mmJSON format | 5i3y.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5i3y_validation.pdf.gz | 720.3 KB | Display | wwPDB validaton report |
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Full document | 5i3y_full_validation.pdf.gz | 723.9 KB | Display | |
Data in XML | 5i3y_validation.xml.gz | 17.7 KB | Display | |
Data in CIF | 5i3y_validation.cif.gz | 25.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/i3/5i3y ftp://data.pdbj.org/pub/pdb/validation_reports/i3/5i3y | HTTPS FTP |
-Related structure data
Related structure data | 5i3vC 5i3wC 5i3xC 5ie1C 1w50S C: citing same article (ref.) S: Starting model for refinement |
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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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Details | Monomer by size exclusion chromatography |
-Components
#1: Protein | Mass: 45822.445 Da / Num. of mol.: 1 / Fragment: UNP residues 43-453 / Mutation: R56K, R57K 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-68K / |
#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: 2.83 Å3/Da / Density % sol: 56.6 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion / pH: 5.5 Details: 1.5 M ammonium sulfate, 0.2 M lithium chloride, 0.1 M bis-tris (pH 5.5) PH range: 5.5-6.0 |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 22-BM / Wavelength: 1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Jul 11, 2015 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.15→50 Å / Num. obs: 29605 / % possible obs: 99.8 % / Observed criterion σ(I): -3 / Redundancy: 10.8 % / Biso Wilson estimate: 26.2 Å2 / Rmerge(I) obs: 0.135 / Net I/av σ(I): 15.3 / Net I/σ(I): 14.3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1W50 Resolution: 2.15→50 Å / Cor.coef. Fo:Fc: 0.942 / Cor.coef. Fo:Fc free: 0.919 / SU B: 8.99 / SU ML: 0.13 / SU R Cruickshank DPI: 0.2001 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.2 / ESU R Free: 0.176 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES: WITH TLS ADDED
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 225.41 Å2 / Biso mean: 40.743 Å2 / Biso min: 8.95 Å2
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Refinement step | Cycle: final / Resolution: 2.15→50 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.151→2.207 Å / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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