+Open data
-Basic information
Entry | Database: PDB / ID: 2vkm | ||||||
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Title | Crystal structure of GRL-8234 bound to BACE (Beta-secretase) | ||||||
Components | BETA-SECRETASE 1 | ||||||
Keywords | HYDROLASE / ALTERNATIVE SPLICING / ASPARTYL PROTEASE / ASPARTIC PROTEASE / GLYCOPROTEIN / TRANSMEMBRANE / BETA SECRETASE / APP / BACE / A-BETA / X- RAY / ZYMOGEN / MEMBRANE / PROTEASE / MEMAPSIN / ALZHEIMER / 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 / dendrite / neuronal cell body / 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: 2.05 Å | ||||||
Authors | Hong, L. / Tang, J. / Ghosh, A.K. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2008 Title: Potent Memapsin 2 (Beta-Secretase) Inhibitors: Design, Synthesis, Protein-Ligand X-Ray Structure, and in Vivo Evaluation. Authors: Ghosh, A.K. / Kumaragurubaran, N. / Hong, L. / Kulkarni, S. / Xu, X. / Miller, H.B. / Reddy, D.S. / Weerasena, V. / Turner, R. / Chang, W. / Koelsch, G. / Tang, J. | ||||||
History |
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Remark 700 | SHEET THE SHEET STRUCTURE OF THIS MOLECULE IS BIFURCATED. IN ORDER TO REPRESENT THIS FEATURE IN ... SHEET THE SHEET STRUCTURE OF THIS MOLECULE IS BIFURCATED. IN ORDER TO REPRESENT THIS FEATURE IN THE SHEET RECORDS BELOW, TWO SHEETS ARE DEFINED. |
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 2vkm.cif.gz | 326.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb2vkm.ent.gz | 267.4 KB | Display | PDB format |
PDBx/mmJSON format | 2vkm.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vk/2vkm ftp://data.pdbj.org/pub/pdb/validation_reports/vk/2vkm | 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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Noncrystallographic symmetry (NCS) | NCS oper: (Code: given / Matrix: (1), |
-Components
#1: Protein | Mass: 43312.805 Da / Num. of mol.: 4 / Fragment: BETA-SECRETASE CATALYTIC DOMAIN, RESIDUES 58-446 Source method: isolated from a genetically manipulated source Details: BETA SECRETASE INHIBITOR / Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21 / References: UniProt: P56817 #2: Chemical | ChemComp-BSD / #3: Water | ChemComp-HOH / | Nonpolymer details | N-(R-CARBOXY-ETHYL)-ALPHA-(S)-(2-PHENYLETHY | |
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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: 2.9 Å3/Da / Density % sol: 56 % / Description: NONE |
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Crystal grow | pH: 6.5 Details: 12% PEG 8000, NACACODYLATE BUFFER, PH 6.5. 15MG/ML PROTEIN CONCENTRATION. ROOM TEMPERATURE. |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Wavelength: 1.5418 |
Detector | Type: MARRESEARCH / Detector: IMAGE PLATE / Date: Jan 30, 2005 / Details: MIRRORS |
Radiation | Monochromator: 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: 2.05→50 Å / Num. obs: 119992 / % possible obs: 99 % / Observed criterion σ(I): 0 / Redundancy: 3.9 % / Biso Wilson estimate: 17.2 Å2 / Rmerge(I) obs: 0.07 / Net I/σ(I): 17 |
Reflection shell | Resolution: 2.01→2.12 Å / Redundancy: 2.5 % / Rmerge(I) obs: 0.39 / Mean I/σ(I) obs: 2.7 / % possible all: 95 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 1FKN Resolution: 2.05→50 Å / Rfactor Rfree error: 0.003 / Data cutoff high absF: 10000 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: MLF
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Solvent computation | Solvent model: FLAT MODEL / Bsol: 50.5921 Å2 / ksol: 0.378055 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 29.4 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 2.05→50 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2→2.13 Å / Rfactor Rfree error: 0.011 / Total num. of bins used: 6
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Xplor file |
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