+Open data
-Basic information
Entry | Database: PDB / ID: 6uwp | ||||||
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Title | BACE-1 in complex with compound #32 | ||||||
Components | Beta-secretase 1 | ||||||
Keywords | HYDROLASE/INHIBITOR / protease / inhibitor / complex / 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 / late endosome / synaptic vesicle / 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 / FOURIER SYNTHESIS / Resolution: 1.29 Å | ||||||
Authors | Hendle, J. / Timm, D.E. | ||||||
Citation | Journal: Bioorg.Med.Chem. / Year: 2020 Title: Preparation and biological evaluation of BACE1 inhibitors: Leveraging trans-cyclopropyl moieties as ligand efficient conformational constraints. Authors: Winneroski, L.L. / Erickson, J.A. / Green, S.J. / Lopez, J.E. / Stout, S.L. / Porter, W.J. / Timm, D.E. / Audia, J.E. / Barberis, M. / Beck, J.P. / Boggs, L.N. / Borders, A.R. / Boyer, R.D. ...Authors: Winneroski, L.L. / Erickson, J.A. / Green, S.J. / Lopez, J.E. / Stout, S.L. / Porter, W.J. / Timm, D.E. / Audia, J.E. / Barberis, M. / Beck, J.P. / Boggs, L.N. / Borders, A.R. / Boyer, R.D. / Brier, R.A. / Hembre, E.J. / Hendle, J. / Garcia-Losada, P. / Minguez, J.M. / Mathes, B.M. / May, P.C. / Monk, S.A. / Rankovic, Z. / Shi, Y. / Watson, B.M. / Yang, Z. / Mergott, D.J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6uwp.cif.gz | 356.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6uwp.ent.gz | 285.6 KB | Display | PDB format |
PDBx/mmJSON format | 6uwp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6uwp_validation.pdf.gz | 394.9 KB | Display | wwPDB validaton report |
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Full document | 6uwp_full_validation.pdf.gz | 396.1 KB | Display | |
Data in XML | 6uwp_validation.xml.gz | 2 KB | Display | |
Data in CIF | 6uwp_validation.cif.gz | 15.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/uw/6uwp ftp://data.pdbj.org/pub/pdb/validation_reports/uw/6uwp | HTTPS FTP |
-Related structure data
Related structure data | 6uvpC 6uvvC 6uvyC 6uwvC 6bfeS 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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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 48970.117 Da / Num. of mol.: 2 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: Chemical | ChemComp-GOL / #4: Chemical | ChemComp-SO4 / #5: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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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: 2.6 Å3/Da / Density % sol: 52.65 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion Details: 100mM Sodium Cacodylate pH 7.4, 12% PEG 8K, 200mM Ammonium Sulfate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 31-ID / Wavelength: 0.97931 Å |
Detector | Type: RAYONIX MX225HE / Detector: CCD / Date: Jun 23, 2011 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97931 Å / Relative weight: 1 |
Reflection | Resolution: 1.29→99.99 Å / Num. obs: 246521 / % possible obs: 97.9 % / Redundancy: 3.7 % / Rmerge(I) obs: 0.086 / Net I/σ(I): 8.3 |
Reflection shell | Resolution: 1.29→1.36 Å / Redundancy: 3.6 % / Rmerge(I) obs: 0.568 / Mean I/σ(I) obs: 2.3 / Num. unique obs: 35194 / % possible all: 96.6 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: 6BFE Resolution: 1.29→30 Å / Cor.coef. Fo:Fc: 0.974 / Cor.coef. Fo:Fc free: 0.966 / SU B: 1.303 / SU ML: 0.024 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.038 / ESU R Free: 0.037 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 73.18 Å2 / Biso mean: 16.661 Å2 / Biso min: 6.11 Å2
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Refinement step | Cycle: final / Resolution: 1.29→30 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.29→1.323 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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