[English] 日本語
Yorodumi- PDB-6wny: Crystal structure of BACE1 in complex with (Z)-fluoro-olefin cont... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6wny | ||||||
---|---|---|---|---|---|---|---|
Title | Crystal structure of BACE1 in complex with (Z)-fluoro-olefin containing compound 15 | ||||||
Components | Beta-secretase 1 | ||||||
Keywords | HYDROLASE/HYDROLASE Inhibitor / aspartic protease / amyloid precursor protein / APP / Alzheimer's disease / inhibitor / HYDROLASE / 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 / detection of mechanical stimulus involved in sensory perception of pain / cellular response to manganese ion / 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 / detection of mechanical stimulus involved in sensory perception of pain / cellular response to manganese ion / amyloid-beta metabolic process / prepulse inhibition / protein serine/threonine kinase binding / cellular response to copper ion / presynaptic modulation of chemical synaptic transmission / multivesicular body / hippocampal mossy fiber to CA3 synapse / response to lead ion / trans-Golgi network / recycling endosome / protein processing / positive regulation of neuron apoptotic process / cellular response to amyloid-beta / late endosome / synaptic vesicle / peptidase activity / amyloid-beta binding / endopeptidase activity / amyloid fibril formation / lysosome / early endosome / aspartic-type endopeptidase activity / 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: 1.86 Å | ||||||
Authors | Whittington, D.A. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2020 Title: The development of a structurally distinct series of BACE1 inhibitors via the (Z)-fluoro-olefin amide bioisosteric replacement. Authors: Frohn, M. / Liu, L. / Siegmund, A.C. / Qian, W. / Amegadzie, A. / Chen, N. / Tan, H. / Hickman, D. / Wood, S. / Wen, P.H. / Bartberger, M.D. / Whittington, D.A. / Allen, J.R. / Bourbeau, M.P. #1: Journal: Bioorg.Med.Chem.Lett. / Year: 2020 Title: The development of a structurally distinct series of BACE1 inhibitors via the (Z)-fluoro-olefin amide bioisosteric replacement Authors: Frohn, M. / Liu, L. / Siegmund, A.C. / Qian, W. / Amegadzie, A. / Chen, N. / Tan, H. / Hickman, D. / Wood, S. / Wen, P.H. / Bartberger, M.D. / Whittington, D.A. / Allen, J.R. / Bourbeau, M.P. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 6wny.cif.gz | 164.5 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6wny.ent.gz | 128.9 KB | Display | PDB format |
PDBx/mmJSON format | 6wny.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6wny_validation.pdf.gz | 723.1 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 6wny_full_validation.pdf.gz | 724.5 KB | Display | |
Data in XML | 6wny_validation.xml.gz | 20.1 KB | Display | |
Data in CIF | 6wny_validation.cif.gz | 31.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wn/6wny ftp://data.pdbj.org/pub/pdb/validation_reports/wn/6wny | HTTPS FTP |
-Related structure data
Similar structure data |
---|
-Links
-Assembly
Deposited unit |
| ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||||||||||||
Unit cell |
| ||||||||||||||||||
Components on special symmetry positions |
|
-Components
#1: Protein | Mass: 45822.445 Da / Num. of mol.: 1 / Mutation: R56K, R57K Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BACE1, BACE, KIAA1149 / Production host: Escherichia coli (E. coli) / References: UniProt: P56817, memapsin 2 | ||||
---|---|---|---|---|---|
#2: Chemical | ChemComp-U64 / | ||||
#3: Chemical | #4: Water | ChemComp-HOH / | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.79 Å3/Da / Density % sol: 55.95 % |
---|---|
Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6.6 Details: 21% PEG 5000 MME, 190 mM ammonium iodide, 190 mM sodium citrate, 3% (v/v) DMSO |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 0.99 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: RAYONIX MX-300 / Detector: CCD / Date: Apr 13, 2016 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.99 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.86→50 Å / Num. obs: 44381 / % possible obs: 99.1 % / Observed criterion σ(I): -3 / Redundancy: 7.1 % / Biso Wilson estimate: 19.23 Å2 / Rmerge(I) obs: 0.066 / Rpim(I) all: 0.026 / Rrim(I) all: 0.071 / Χ2: 0.913 / Net I/σ(I): 8.3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
|
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: proprietary structure Resolution: 1.86→34.9 Å / SU ML: 0.2 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 19.41
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 110.6 Å2 / Biso mean: 27.4 Å2 / Biso min: 7.51 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.86→34.9 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0
|