[English] 日本語
Yorodumi- PDB-3h0b: Discovery of aminoheterocycles as a novel beta-secretase inhibito... -
+Open data
-Basic information
Entry | Database: PDB / ID: 3h0b | ||||||
---|---|---|---|---|---|---|---|
Title | Discovery of aminoheterocycles as a novel beta-secretase inhibitor class | ||||||
Components | Beta-secretase 1 | ||||||
Keywords | HYDROLASE / Aspartyl Protease / Alternative splicing / Disulfide bond / Glycoprotein / Membrane / Polymorphism / Protease / Transmembrane / Zymogen | ||||||
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 / 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 / lysosome / aspartic-type endopeptidase activity / 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: 2.7 Å | ||||||
Authors | Allison, T.J. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2009 Title: Discovery of aminoheterocycles as a novel beta-secretase inhibitor class: pH dependence on binding activity part 1. Authors: Stachel, S.J. / Coburn, C.A. / Rush, D. / Jones, K.L. / Zhu, H. / Rajapakse, H. / Graham, S.L. / Simon, A. / Katharine Holloway, M. / Allison, T.J. / Munshi, S.K. / Espeseth, A.S. / Zuck, P. ...Authors: Stachel, S.J. / Coburn, C.A. / Rush, D. / Jones, K.L. / Zhu, H. / Rajapakse, H. / Graham, S.L. / Simon, A. / Katharine Holloway, M. / Allison, T.J. / Munshi, S.K. / Espeseth, A.S. / Zuck, P. / Colussi, D. / Wolfe, A. / Pietrak, B.L. / Lai, M.T. / Vacca, J.P. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 3h0b.cif.gz | 231.2 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb3h0b.ent.gz | 185.7 KB | Display | PDB format |
PDBx/mmJSON format | 3h0b.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/h0/3h0b ftp://data.pdbj.org/pub/pdb/validation_reports/h0/3h0b | HTTPS FTP |
---|
-Related structure data
Related structure data | 1tqfS S: Starting model for refinement |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||||||||||||||||||||||||||||||
2 |
| ||||||||||||||||||||||||||||||||||||
3 |
| ||||||||||||||||||||||||||||||||||||
Unit cell |
| ||||||||||||||||||||||||||||||||||||
Components on special symmetry positions |
| ||||||||||||||||||||||||||||||||||||
Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
|
-Components
#1: Protein | Mass: 45238.891 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BACE, BACE1, beta-secretase, KIAA1149 / Production host: Escherichia coli (E. coli) / References: UniProt: P56817, memapsin 2 #2: Chemical | #3: Water | ChemComp-HOH / | |
---|
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.81 Å3/Da / Density % sol: 56.23 % |
---|---|
Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7.5 Details: 1.5M Lithium Sulfate, 0.1M HEPES pH 7.5; crystals were soaked in 1.5M Lithium Sulfate, 0.1M Na Citrate, pH 5.0, 0.5mM inhibitor, VAPOR DIFFUSION, SITTING DROP, temperature 293K |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 4r / Detector: CCD / Date: Sep 14, 2004 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.7→47.25 Å / Num. obs: 41217 / % possible obs: 99.9 % / Redundancy: 3.8 % / Rmerge(I) obs: 0.078 / Χ2: 1.024 / Net I/σ(I): 17.402 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
|
-Processing
Software |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1TQF Resolution: 2.7→47.25 Å / Cor.coef. Fo:Fc: 0.928 / Cor.coef. Fo:Fc free: 0.91 / WRfactor Rfree: 0.243 / WRfactor Rwork: 0.211 / Occupancy max: 1 / Occupancy min: 0.5 / FOM work R set: 0.801 / SU B: 13.569 / SU ML: 0.27 / SU R Cruickshank DPI: 1.071 / SU Rfree: 0.332 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 1.071 / ESU R Free: 0.332 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS; U VALUES: REFINED INDIVIDUALLY
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 94.7 Å2 / Biso mean: 53.312 Å2 / Biso min: 24.72 Å2
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.7→47.25 Å
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints NCS | Dom-ID: 1 / Ens-ID: 1 / Number: 2932 / Refine-ID: X-RAY DIFFRACTION
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 2.7→2.771 Å / Total num. of bins used: 20
|