[English] 日本語
Yorodumi- PDB-4r93: BACE-1 in complex with (R)-4-(2-cyclohexylethyl)-1-methyl-5-oxo-4... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4r93 | ||||||
---|---|---|---|---|---|---|---|
Title | BACE-1 in complex with (R)-4-(2-cyclohexylethyl)-1-methyl-5-oxo-4-(((1S,3R)-3-(3-phenylureido)cyclohexyl)methyl)imidazolidin-2-iminium | ||||||
Components | Beta-secretase 1 | ||||||
Keywords | Hydrolase/Hydrolase inhibitor / Aspartic 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 / 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 / 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 / FOURIER SYNTHESIS / Resolution: 1.71 Å | ||||||
Authors | Orth, P. / Strickland, C. / Caldwell, J.P. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2014 Title: Discovery of potent iminoheterocycle BACE1 inhibitors. Authors: Caldwell, J.P. / Mazzola, R.D. / Durkin, J. / Chen, J. / Chen, X. / Favreau, L. / Kennedy, M. / Kuvelkar, R. / Lee, J. / McHugh, N. / McKittrick, B. / Orth, P. / Stamford, A. / Strickland, C. ...Authors: Caldwell, J.P. / Mazzola, R.D. / Durkin, J. / Chen, J. / Chen, X. / Favreau, L. / Kennedy, M. / Kuvelkar, R. / Lee, J. / McHugh, N. / McKittrick, B. / Orth, P. / Stamford, A. / Strickland, C. / Voigt, J. / Wang, L. / Zhang, L. / Zhang, Q. / Zhu, Z. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 4r93.cif.gz | 180.7 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb4r93.ent.gz | 148.1 KB | Display | PDB format |
PDBx/mmJSON format | 4r93.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/r9/4r93 ftp://data.pdbj.org/pub/pdb/validation_reports/r9/4r93 | HTTPS FTP |
---|
-Related structure data
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
2 |
| ||||||||
Unit cell |
|
-Components
#1: Protein | Mass: 46249.926 Da / Num. of mol.: 2 / Fragment: UNP residues 41-454 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 | #4: Water | ChemComp-HOH / | |
---|
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.73 Å3/Da / Density % sol: 55.02 % |
---|---|
Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7 Details: 20% PEG 3350, 200mM K/Na tatrate, 100mM Hepes, pH 7.0, vapor diffusion, hanging drop, temperature 277K |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Diffraction source | Source: ROTATING ANODE / Type: RIGAKU RU200 / Wavelength: 1.54178 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: RIGAKU RAXIS IV / Detector: IMAGE PLATE / Details: mirror | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Monochromator: Mirror / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1.54178 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.71→20 Å / Num. all: 109961 / Num. obs: 109796 / % possible obs: 99.9 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Rmerge(I) obs: 0.072 / Χ2: 1 / Net I/σ(I): 8.4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
|
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: FOURIER SYNTHESIS / Resolution: 1.71→19.88 Å / Cor.coef. Fo:Fc: 0.9542 / Cor.coef. Fo:Fc free: 0.9382 / Occupancy max: 1 / Occupancy min: 1 / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 88.14 Å2 / Biso mean: 19.1516 Å2 / Biso min: 5.87 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine analyze | Luzzati coordinate error obs: 0.179 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.71→19.88 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 1.71→1.75 Å / Total num. of bins used: 20
|