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Yorodumi- PDB-2p4j: Crystal structure of beta-secretase bond to an inhibitor with Iso... -
+Open data
-Basic information
Entry | Database: PDB / ID: 2p4j | ||||||
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Title | Crystal structure of beta-secretase bond to an inhibitor with Isophthalamide Derivatives at P2-P3 | ||||||
Components | Beta-secretase 1 | ||||||
Keywords | HYDROLASE / beta-secretase / memapsin / BACE / asp / aspartic protease / acid protease / Alzheimer's disease / drug design / structure based drug design | ||||||
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 / MOLECULAR REPLACEMENT / Resolution: 2.5 Å | ||||||
Authors | Hong, L. / Ghosh, A.K. / Tang, J. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2007 Title: Design, synthesis, and X-ray structure of potent memapsin 2 (beta-secretase) inhibitors with isophthalamide derivatives as the P2-P3-ligands. Authors: Ghosh, A.K. / Kumaragurubaran, N. / Hong, L. / Kulkarni, S.S. / Xu, X. / Chang, W. / Weerasena, V. / Turner, R. / Koelsch, G. / Bilcer, G. / Tang, J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 2p4j.cif.gz | 319.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb2p4j.ent.gz | 261.1 KB | Display | PDB format |
PDBx/mmJSON format | 2p4j.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/p4/2p4j ftp://data.pdbj.org/pub/pdb/validation_reports/p4/2p4j | HTTPS FTP |
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-Related structure data
Related structure data | 1fknS S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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3 |
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4 |
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Unit cell |
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-Components
#1: Protein | Mass: 43312.805 Da / Num. of mol.: 4 / Fragment: Catalytic domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BACE1, BACE / Plasmid: PET11 / Species (production host): Escherichia coli / Production host: Escherichia coli BL21 (bacteria) / Strain (production host): BL21 / References: UniProt: P56817, memapsin 2 #2: Chemical | ChemComp-23I / #3: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.83 Å3/Da / Density % sol: 56.49 % |
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Crystal grow | Temperature: 290 K / Method: vapor diffusion, hanging drop / pH: 6.5 Details: CRYSTALLIZATION CONDITIONS: APO ENZYME CRYSTAL WAS OBTAINED AT 15 mg/ml, 13% PEG 8000, PH 6.5 IN SODIUM CACODYLATE BUFFER. THE APO ENZYME CRYSTAL WAS SOAKED IN CONCENTRATED INHIBITOR ...Details: CRYSTALLIZATION CONDITIONS: APO ENZYME CRYSTAL WAS OBTAINED AT 15 mg/ml, 13% PEG 8000, PH 6.5 IN SODIUM CACODYLATE BUFFER. THE APO ENZYME CRYSTAL WAS SOAKED IN CONCENTRATED INHIBITOR SOLUTION TO MAKE THE ENZYME/INHIBITOR COMPLEX CRYSTAL FOR X-RAY DATA COLLECTION, VAPOR DIFFUSION, HANGING DROP, temperature 290K |
-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 300 mm plate / Detector: IMAGE PLATE / Date: Jul 3, 2006 / Details: mirrors |
Radiation | Monochromator: Ni MIRROR + Ni FILTER / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 2.5→50 Å / Num. all: 66606 / Num. obs: 66290 / % possible obs: 97.6 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 3.9 % / Rmerge(I) obs: 0.11 / Χ2: 1.065 / Net I/σ(I): 8.1 |
Reflection shell | Resolution: 2.5→2.59 Å / Rmerge(I) obs: 0.611 / Mean I/σ(I) obs: 1.9 / Num. unique all: 5760 / Χ2: 1.029 / % possible all: 85.6 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB entry 1FKN Resolution: 2.5→50 Å / FOM work R set: 0.793 / Isotropic thermal model: isotropic / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
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Solvent computation | Bsol: 37.395 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 38.821 Å2
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Refinement step | Cycle: LAST / Resolution: 2.5→50 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 50
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Xplor file |
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