+Open data
-Basic information
Entry | Database: PDB / ID: 5clm | ||||||
---|---|---|---|---|---|---|---|
Title | 1,4-Oxazine BACE1 inhibitors | ||||||
Components | Beta-secretase 1 | ||||||
Keywords | HYDROLASE / BACE1 PROTEASE Inhibitor / orally bioavailable / brain penetrant / PROTEROS BIOSTRUCTURES GMBH | ||||||
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 / amyloid-beta metabolic process ...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 / amyloid-beta metabolic process / detection of mechanical stimulus involved in sensory perception of pain / 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 / dendrite / neuronal cell body / 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: 2.61 Å | ||||||
Authors | Rombouts, F. / Tresadern, G. / Delgado, O. / Martinez Lamenca, C. / Van Gool, M. / Garcia-Molina, A. / Alonso De Diego, S. / Oehlrich, D. / Prokopcova, H. / Alonso, J.M. ...Rombouts, F. / Tresadern, G. / Delgado, O. / Martinez Lamenca, C. / Van Gool, M. / Garcia-Molina, A. / Alonso De Diego, S. / Oehlrich, D. / Prokopcova, H. / Alonso, J.M. / Austin, N. / Borghys, H. / Van Brandt, S. / Surkyn, M. / De Cleyn, M. / Vos, A. / Alexander, R. / MacDonald, G. / Moechars, D. / Trabanco, A. / Gijsen, H. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2015 Title: 1,4-Oxazine beta-Secretase 1 (BACE1) Inhibitors: From Hit Generation to Orally Bioavailable Brain Penetrant Leads. Authors: Rombouts, F.J. / Tresadern, G. / Delgado, O. / Martinez-Lamenca, C. / Van Gool, M. / Garcia-Molina, A. / Alonso de Diego, S.A. / Oehlrich, D. / Prokopcova, H. / Alonso, J.M. / Austin, N. / ...Authors: Rombouts, F.J. / Tresadern, G. / Delgado, O. / Martinez-Lamenca, C. / Van Gool, M. / Garcia-Molina, A. / Alonso de Diego, S.A. / Oehlrich, D. / Prokopcova, H. / Alonso, J.M. / Austin, N. / Borghys, H. / Van Brandt, S. / Surkyn, M. / De Cleyn, M. / Vos, A. / Alexander, R. / Macdonald, G. / Moechars, D. / Gijsen, H. / Trabanco, A.A. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 5clm.cif.gz | 88.1 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb5clm.ent.gz | 69.4 KB | Display | PDB format |
PDBx/mmJSON format | 5clm.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cl/5clm ftp://data.pdbj.org/pub/pdb/validation_reports/cl/5clm | HTTPS FTP |
---|
-Related structure data
Similar structure data |
---|
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
#1: Protein | Mass: 44628.051 Da / Num. of mol.: 1 / Fragment: PROTEASE, UNP residues 46-446 / Mutation: R11T, R12T 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 | ChemComp-52K / | ||||
#3: Chemical | #4: Chemical | ChemComp-CL / | #5: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.87 Å3/Da / Density % sol: 57.11 % |
---|---|
Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / Details: 12% (m/v) PEG4000, 100mM MES/NaOH pH 5.5 / PH range: 5.5 |
-Data collection
Diffraction | Mean temperature: 100 K |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jun 2, 2010 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.6→87.32 Å / Num. obs: 16235 / % possible obs: 99 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 15.3 % / Biso Wilson estimate: 54.499 Å2 / Rmerge(I) obs: 0.093 / Net I/σ(I): 24.85 |
Reflection shell | Resolution: 2.6→2.77 Å / Redundancy: 15.6 % / Rmerge(I) obs: 0.797 / % possible all: 94.5 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.61→87.32 Å / Cor.coef. Fo:Fc: 0.945 / Cor.coef. Fo:Fc free: 0.909 / SU B: 9.292 / SU ML: 0.201 / Cross valid method: THROUGHOUT / ESU R: 0.499 / ESU R Free: 0.296 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 49.026 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.61→87.32 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
|