+Open data
-Basic information
Entry | Database: PDB / ID: 7myu | ||||||
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Title | BACE-1 in complex with compound #22 | ||||||
Components | Beta-secretase 1 | ||||||
Keywords | HYDROLASE/HYDROLASE INHIBITOR / 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 / 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 / MOLECULAR REPLACEMENT / Resolution: 1.94 Å | ||||||
Authors | Hendle, J. / Timm, D.E. / Stout, S.L. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2021 Title: Discovery and Early Clinical Development of LY3202626, a Low-Dose, CNS-Penetrant BACE Inhibitor. Authors: McKinzie, D.L. / Winneroski, L.L. / Green, S.J. / Hembre, E.J. / Erickson, J.A. / Willis, B.A. / Monk, S.A. / Aluise, C.D. / Baker, T.K. / Lopez, J.E. / Hendle, J. / Beck, J.P. / Brier, R.A. ...Authors: McKinzie, D.L. / Winneroski, L.L. / Green, S.J. / Hembre, E.J. / Erickson, J.A. / Willis, B.A. / Monk, S.A. / Aluise, C.D. / Baker, T.K. / Lopez, J.E. / Hendle, J. / Beck, J.P. / Brier, R.A. / Boggs, L.N. / Borders, A.R. / Cocke, P.J. / Garcia-Losada, P. / Lowe, S.L. / Mathes, B.M. / May, P.C. / Porter, W.J. / Stout, S.L. / Timm, D.E. / 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 | 7myu.cif.gz | 187.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7myu.ent.gz | 146.1 KB | Display | PDB format |
PDBx/mmJSON format | 7myu.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7myu_validation.pdf.gz | 980.2 KB | Display | wwPDB validaton report |
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Full document | 7myu_full_validation.pdf.gz | 963.8 KB | Display | |
Data in XML | 7myu_validation.xml.gz | 36.5 KB | Display | |
Data in CIF | 7myu_validation.cif.gz | 55.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/my/7myu ftp://data.pdbj.org/pub/pdb/validation_reports/my/7myu | HTTPS FTP |
-Related structure data
Related structure data | 7myiC 7myrC 6uvpS 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-SO4 / | #4: 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: 2.62 Å3/Da / Density % sol: 53.07 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop 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: Mar 14, 2013 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97931 Å / Relative weight: 1 |
Reflection | Resolution: 1.94→34 Å / Num. obs: 76824 / % possible obs: 99.7 % / Redundancy: 7.2 % / Rmerge(I) obs: 0.155 / Net I/σ(I): 7.8 |
Reflection shell | Resolution: 1.94→2.04 Å / Redundancy: 7.1 % / Rmerge(I) obs: 0.708 / Mean I/σ(I) obs: 2.5 / Num. unique obs: 11029 / % possible all: 99.5 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6UVP Resolution: 1.94→30 Å / Cor.coef. Fo:Fc: 0.963 / Cor.coef. Fo:Fc free: 0.946 / SU B: 3.817 / SU ML: 0.104 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.138 / ESU R Free: 0.134 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: 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: 111.79 Å2 / Biso mean: 24.129 Å2 / Biso min: 8.58 Å2
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Refinement step | Cycle: final / Resolution: 1.94→30 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.94→1.99 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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