+Open data
-Basic information
Entry | Database: PDB / ID: 3udh | ||||||
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Title | Crystal Structure of BACE with Compound 1 | ||||||
Components | Beta-secretase 1 | ||||||
Keywords | HYDROLASE/HYDROLASE INHIBITOR / 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 / amyloid-beta metabolic process / cellular response to manganese ion / detection of mechanical stimulus involved in sensory perception of pain ...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 / amyloid-beta metabolic process / cellular response to manganese ion / detection of mechanical stimulus involved in sensory perception of pain / 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 / protein processing / recycling endosome / cellular response to amyloid-beta / positive regulation of neuron apoptotic process / late endosome / synaptic vesicle / peptidase activity / amyloid-beta binding / endopeptidase activity / amyloid fibril formation / aspartic-type endopeptidase activity / early endosome / lysosome / 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 / RIGID BODY REFINEMENT / Resolution: 1.7 Å | ||||||
Authors | Efremov, I.V. / Vajdos, F.F. / Borzilleri, K. / Capetta, S. / Dorff, P. / Dutra, J. / Mansour, M. / Oborski, C. / O'Connell, T. / O'Sullivan, T.J. ...Efremov, I.V. / Vajdos, F.F. / Borzilleri, K. / Capetta, S. / Dorff, P. / Dutra, J. / Mansour, M. / Oborski, C. / O'Connell, T. / O'Sullivan, T.J. / Pandit, J. / Wang, H. / Withka, J. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2012 Title: Discovery and optimization of a novel spiropyrrolidine inhibitor of {beta}-secretase (BACE1) through fragment-based drug design. Authors: Efremov, I.V. / Vajdos, F.F. / Borzilleri, K.A. / Capetta, S. / Chen, H. / Dorff, P.H. / Dutra, J.K. / Goldstein, S.W. / Mansour, M. / McColl, A. / Noell, S. / Oborski, C.E. / O'Connell, T.N. ...Authors: Efremov, I.V. / Vajdos, F.F. / Borzilleri, K.A. / Capetta, S. / Chen, H. / Dorff, P.H. / Dutra, J.K. / Goldstein, S.W. / Mansour, M. / McColl, A. / Noell, S. / Oborski, C.E. / O'Connell, T.N. / O'Sullivan, T.J. / Pandit, J. / Wang, H. / Wei, B. / Withka, J.M. #1: Journal: Protein Pept.Lett. / Year: 2008 Title: High yield expression of human BACE constructs in Escherichia coli for refolding, purification, and high resolution diffracting crystal forms. Authors: Tomasselli, A.G. / Paddock, D.J. / Emmons, T.L. / Mildner, A.M. / Leone, J.W. / Lull, J.M. / Cialdella, J.I. / Prince, D.B. / Fischer, H.D. / Heinrikson, R.L. / Benson, T.E. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3udh.cif.gz | 96 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3udh.ent.gz | 76.6 KB | Display | PDB format |
PDBx/mmJSON format | 3udh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 3udh_validation.pdf.gz | 466.1 KB | Display | wwPDB validaton report |
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Full document | 3udh_full_validation.pdf.gz | 470.2 KB | Display | |
Data in XML | 3udh_validation.xml.gz | 20.3 KB | Display | |
Data in CIF | 3udh_validation.cif.gz | 30 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ud/3udh ftp://data.pdbj.org/pub/pdb/validation_reports/ud/3udh | HTTPS FTP |
-Related structure data
Related structure data | 3udjC 3udkC 3udmC 3udnC 3udpC 3udqC 3udrC 3udyC C: citing same article (ref.) |
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Similar 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: 45156.730 Da / Num. of mol.: 1 / Fragment: UNP residues 58-453 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BACE1, BACE, KIAA1149 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P56817, memapsin 2 | ||||
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#2: Chemical | ChemComp-091 / ( | ||||
#3: Chemical | ChemComp-EDO / #4: Chemical | ChemComp-ZN / | #5: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.14 Å3/Da / Density % sol: 42.51 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion Details: protein in sodium borate, pH 8.5, reservoir: 30% PEG200, 0.1 M sodium acetate, pH 5.2-5.4, VAPOR DIFFUSION, temperature 298K |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-BM / Wavelength: 1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: MAR CCD 165 mm / Detector: CCD / Date: Apr 10, 2008 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Monochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.7→46.03 Å / Num. obs: 41969 / % possible obs: 98.7 % / Redundancy: 4.73 % / Rmerge(I) obs: 0.043 / Net I/σ(I): 13.1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Processing
Software |
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Refinement | Method to determine structure: RIGID BODY REFINEMENT / Resolution: 1.7→46.03 Å / Cor.coef. Fo:Fc: 0.963 / Cor.coef. Fo:Fc free: 0.943 / Occupancy max: 1 / Occupancy min: 0.5 / SU B: 2.647 / SU ML: 0.086 / Cross valid method: THROUGHOUT / ESU R: 0.125 / ESU R Free: 0.124 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 24.283 Å2
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Refinement step | Cycle: LAST / Resolution: 1.7→46.03 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.7→1.749 Å / Total num. of bins used: 20
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