+Open data
-Basic information
Entry | Database: PDB / ID: 4dpi | ||||||
---|---|---|---|---|---|---|---|
Title | BACE-1 in complex with HEA-macrocyclic inhibitor, MV078512 | ||||||
Components | Beta-secretase 1 | ||||||
Keywords | Hydrolase/Hydrolase inhibitor / BACE1 / ASP2 / BACE / macrocycle / 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 / 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 / molecular replacement / Resolution: 1.9 Å | ||||||
Authors | Lindberg, J. / Borkakoti, N. / Derbyshire, D. | ||||||
Citation | Journal: Bioorg.Med.Chem. / Year: 2012 Title: Highly potent macrocyclic BACE-1 inhibitors incorporating a hydroxyethylamine core: design, synthesis and X-ray crystal structures of enzyme inhibitor complexes. Authors: Sandgren, V. / Agback, T. / Johansson, P.O. / Lindberg, J. / Kvarnstrom, I. / Samuelsson, B. / Belda, O. / Dahlgren, A. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 4dpi.cif.gz | 163.3 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb4dpi.ent.gz | 134.8 KB | Display | PDB format |
PDBx/mmJSON format | 4dpi.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dp/4dpi ftp://data.pdbj.org/pub/pdb/validation_reports/dp/4dpi | HTTPS FTP |
---|
-Related structure data
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
#1: Protein | Mass: 43601.195 Da / Num. of mol.: 1 / Fragment: unp residues 57-446 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BACE1, BACE, KIAA1149 / Plasmid: pET21 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P56817, memapsin 2 |
---|---|
#2: Chemical | ChemComp-0N1 / ( |
#3: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.18 Å3/Da / Density % sol: 43.63 % |
---|---|
Crystal grow | Temperature: 291 K / Method: vapor diffusion / pH: 4.5 Details: 18% PEG 1000, 0.1 Na-Acetate pH4.5, 5% Glycerol, vapor diffusion, temperature 291K |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID23-2 / Wavelength: 0.976 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Jun 29, 2011 / Details: Mirrors | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Monochromator: Graphite / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.976 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.9→61.843 Å / Num. all: 31429 / Num. obs: 31429 / % possible obs: 99.7 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2 / Redundancy: 4.6 % / Rsym value: 0.079 / Net I/σ(I): 13.5 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
|
-Phasing
Phasing | Method: molecular replacement | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Phasing MR | Rfactor: 36.68 / Model details: Phaser MODE: MR_AUTO
|
-Processing
Software |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.9→44.03 Å / Cor.coef. Fo:Fc: 0.953 / Cor.coef. Fo:Fc free: 0.923 / WRfactor Rfree: 0.2248 / WRfactor Rwork: 0.176 / Occupancy max: 1 / Occupancy min: 0.3 / FOM work R set: 0.8659 / SU B: 6.745 / SU ML: 0.092 / SU R Cruickshank DPI: 0.1508 / SU Rfree: 0.1425 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.151 / ESU R Free: 0.142 / 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: 1.4 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 60.84 Å2 / Biso mean: 18.2156 Å2 / Biso min: 3.7 Å2
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.9→44.03 Å
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 1.9→1.949 Å / Total num. of bins used: 20
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS params. | Method: refined / Origin x: 2.2463 Å / Origin y: 1.5409 Å / Origin z: 14.9754 Å
|