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Yorodumi- PDB-4acx: Aminoimidazoles as BACE-1 Inhibitors. X-RAY CRYSTAL STRUCTURE OF ... -
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-Basic information
Entry | Database: PDB / ID: 4acx | ||||||
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Title | Aminoimidazoles as BACE-1 Inhibitors. X-RAY CRYSTAL STRUCTURE OF BETA SECRETASE COMPLEXED WITH COMPOUND 23 | ||||||
Components | BETA-SECRETASE 1 | ||||||
Keywords | HYDROLASE / ALZHEIMER'S DISEASE | ||||||
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 / MOLECULAR REPLACEMENT / Resolution: 2 Å | ||||||
Authors | Swahn, B. / Holenz, J. / Kihlstrom, J. / Kolmodin, K. / Lindstrom, J. / Plobeck, N. / Rotticci, D. / Sehgelmeble, F. / Sundstrom, M. / von Berg, S. ...Swahn, B. / Holenz, J. / Kihlstrom, J. / Kolmodin, K. / Lindstrom, J. / Plobeck, N. / Rotticci, D. / Sehgelmeble, F. / Sundstrom, M. / von Berg, S. / Falting, J. / Georgievska, B. / Gustavsson, S. / Neelissen, J. / Ek, M. / Olsson, L.L. / Berg, S. | ||||||
Citation | Journal: Bioorg. Med. Chem. Lett. / Year: 2012 Title: Aminoimidazoles as BACE-1 inhibitors: the challenge to achieve in vivo brain efficacy. Authors: Swahn, B.M. / Holenz, J. / Kihlstrom, J. / Kolmodin, K. / Lindstrom, J. / Plobeck, N. / Rotticci, D. / Sehgelmeble, F. / Sundstrom, M. / Berg, S.v. / Falting, J. / Georgievska, B. / ...Authors: Swahn, B.M. / Holenz, J. / Kihlstrom, J. / Kolmodin, K. / Lindstrom, J. / Plobeck, N. / Rotticci, D. / Sehgelmeble, F. / Sundstrom, M. / Berg, S.v. / Falting, J. / Georgievska, B. / Gustavsson, S. / Neelissen, J. / Ek, M. / Olsson, L.L. / Berg, S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4acx.cif.gz | 95.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4acx.ent.gz | 71.3 KB | Display | PDB format |
PDBx/mmJSON format | 4acx.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ac/4acx ftp://data.pdbj.org/pub/pdb/validation_reports/ac/4acx | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 45822.445 Da / Num. of mol.: 1 / Fragment: RESIDUES 43-453 / Mutation: YES Source method: isolated from a genetically manipulated source Details: PROPEPTIDE NUMBERED 484-502 / Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli) / References: UniProt: P56817, memapsin 2 |
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#2: Chemical | ChemComp-ACT / |
#3: Chemical | ChemComp-S8Z / ( |
#4: Water | ChemComp-HOH / |
Compound details | ENGINEERED |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.07 Å3/Da / Density % sol: 41 % / Description: NONE |
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Crystal grow | pH: 5 Details: 11% PEG6K, 90 MM NAAC PH 5.0, 18 MM TRIS PH 8.5, 135 MM NACL |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU RU300 / Wavelength: 1.5418 |
Detector | Type: MAR scanner 345 mm plate / Detector: IMAGE PLATE / Date: Feb 19, 2008 / Details: MIRRORS |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 2→43.6 Å / Num. obs: 25609 / % possible obs: 93.6 % / Observed criterion σ(I): 1 / Redundancy: 3.1 % / Biso Wilson estimate: 22.45 Å2 / Rmerge(I) obs: 0.1 / Net I/σ(I): 10.1 |
Reflection shell | Resolution: 2→2.05 Å / Redundancy: 3.1 % / Rmerge(I) obs: 0.4 / Mean I/σ(I) obs: 2.7 / % possible all: 99.6 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PREVIOUSLY DETERMINED BACE-1 STRUCTURE Resolution: 2→43.64 Å / Cor.coef. Fo:Fc: 0.9257 / Cor.coef. Fo:Fc free: 0.9049 / SU R Cruickshank DPI: 0.21 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.226 / SU Rfree Blow DPI: 0.179 / SU Rfree Cruickshank DPI: 0.175 Details: IDEAL-DIST CONTACT TERM CONTACT SETUP. ALL ATOMS HAVE CCP4 ATOM TYPE FROM LIBRARY
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Displacement parameters | Biso mean: 25.41 Å2
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Refine analyze | Luzzati coordinate error obs: 0.244 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2→43.64 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2→2.08 Å / Total num. of bins used: 13
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