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- PDB-1owt: Structure of the Alzheimer's disease amyloid precursor protein co... -

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Basic information

Entry
Database: PDB / ID: 1owt
TitleStructure of the Alzheimer's disease amyloid precursor protein copper binding domain
ComponentsAmyloid beta A4 protein
KeywordsAPOPTOSIS / beta-alpha-beta-beta
Function / homology
Function and homology information


cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of Wnt signaling pathway / regulation of synapse structure or activity / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / signaling receptor activator activity / axon midline choice point recognition ...cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of Wnt signaling pathway / regulation of synapse structure or activity / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / signaling receptor activator activity / axon midline choice point recognition / smooth endoplasmic reticulum calcium ion homeostasis / astrocyte activation involved in immune response / regulation of spontaneous synaptic transmission / mating behavior / NMDA selective glutamate receptor signaling pathway / ciliary rootlet / Lysosome Vesicle Biogenesis / PTB domain binding / Golgi-associated vesicle / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / positive regulation of amyloid fibril formation / neuron remodeling / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / nuclear envelope lumen / suckling behavior / COPII-coated ER to Golgi transport vesicle / dendrite development / presynaptic active zone / modulation of excitatory postsynaptic potential / TRAF6 mediated NF-kB activation / Advanced glycosylation endproduct receptor signaling / neuromuscular process controlling balance / The NLRP3 inflammasome / negative regulation of long-term synaptic potentiation / regulation of presynapse assembly / transition metal ion binding / regulation of multicellular organism growth / negative regulation of neuron differentiation / intracellular copper ion homeostasis / ECM proteoglycans / spindle midzone / positive regulation of T cell migration / smooth endoplasmic reticulum / Purinergic signaling in leishmaniasis infection / protein serine/threonine kinase binding / regulation of peptidyl-tyrosine phosphorylation / clathrin-coated pit / positive regulation of chemokine production / forebrain development / Notch signaling pathway / neuron projection maintenance / positive regulation of G2/M transition of mitotic cell cycle / Mitochondrial protein degradation / positive regulation of protein metabolic process / positive regulation of calcium-mediated signaling / ionotropic glutamate receptor signaling pathway / cholesterol metabolic process / positive regulation of glycolytic process / extracellular matrix organization / positive regulation of mitotic cell cycle / response to interleukin-1 / axonogenesis / adult locomotory behavior / trans-Golgi network membrane / platelet alpha granule lumen / positive regulation of peptidyl-threonine phosphorylation / dendritic shaft / learning / positive regulation of interleukin-1 beta production / positive regulation of long-term synaptic potentiation / central nervous system development / endosome lumen / locomotory behavior / astrocyte activation / Post-translational protein phosphorylation / positive regulation of JNK cascade / microglial cell activation / synapse organization / regulation of long-term neuronal synaptic plasticity / serine-type endopeptidase inhibitor activity / TAK1-dependent IKK and NF-kappa-B activation / visual learning / neuromuscular junction / recycling endosome / cognition / Golgi lumen / positive regulation of inflammatory response / positive regulation of interleukin-6 production / neuron cellular homeostasis / positive regulation of non-canonical NF-kappaB signal transduction / endocytosis / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / cellular response to amyloid-beta / G2/M transition of mitotic cell cycle / positive regulation of tumor necrosis factor production / neuron projection development / cell-cell junction / synaptic vesicle / Platelet degranulation / apical part of cell
Similarity search - Function
Amyloidogenic glycoprotein, copper-binding domain / Amyloidogenic glycoprotein, copper-binding / Amyloidogenic glycoprotein, copper-binding domain conserved site / Amyloidogenic glycoprotein, copper-binding domain superfamily / Copper-binding of amyloid precursor, CuBD / Amyloid precursor protein (APP) copper-binding (CuBD) domain signature. / Amyloidogenic glycoprotein, amyloid-beta peptide superfamily / Beta-amyloid peptide (beta-APP) / Amyloidogenic glycoprotein, amyloid-beta peptide / Beta-amyloid precursor protein C-terminal ...Amyloidogenic glycoprotein, copper-binding domain / Amyloidogenic glycoprotein, copper-binding / Amyloidogenic glycoprotein, copper-binding domain conserved site / Amyloidogenic glycoprotein, copper-binding domain superfamily / Copper-binding of amyloid precursor, CuBD / Amyloid precursor protein (APP) copper-binding (CuBD) domain signature. / Amyloidogenic glycoprotein, amyloid-beta peptide superfamily / Beta-amyloid peptide (beta-APP) / Amyloidogenic glycoprotein, amyloid-beta peptide / Beta-amyloid precursor protein C-terminal / Amyloidogenic glycoprotein, intracellular domain, conserved site / Beta-amyloid precursor protein C-terminus / Amyloid precursor protein (APP) intracellular domain signature. / Amyloidogenic glycoprotein, extracellular / Amyloidogenic glycoprotein, heparin-binding / Amyloidogenic glycoprotein, E2 domain / E2 domain superfamily / Amyloidogenic glycoprotein, heparin-binding domain superfamily / Amyloid A4 N-terminal heparin-binding / E2 domain of amyloid precursor protein / Amyloid precursor protein (APP) E1 domain profile. / Amyloid precursor protein (APP) E2 domain profile. / amyloid A4 / Amyloidogenic glycoprotein / Proteinase inhibitor I2, Kunitz, conserved site / Pancreatic trypsin inhibitor (Kunitz) family signature. / BPTI/Kunitz family of serine protease inhibitors. / Pancreatic trypsin inhibitor Kunitz domain / Kunitz/Bovine pancreatic trypsin inhibitor domain / Pancreatic trypsin inhibitor (Kunitz) family profile. / Pancreatic trypsin inhibitor Kunitz domain superfamily / Dna Ligase; domain 1 / PH-like domain superfamily / 2-Layer Sandwich / Alpha Beta
Similarity search - Domain/homology
Amyloid-beta precursor protein
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodSOLUTION NMR / distance geometry, simulated annealing
AuthorsBarnham, K.J. / McKinstry, W.J. / Multhaup, G. / Galatis, D. / Morton, C.J. / Curtain, C.C. / Williamson, N.A. / White, A.R. / Hinds, M.G. / Norton, R.S. ...Barnham, K.J. / McKinstry, W.J. / Multhaup, G. / Galatis, D. / Morton, C.J. / Curtain, C.C. / Williamson, N.A. / White, A.R. / Hinds, M.G. / Norton, R.S. / Beyreuther, K. / Masters, C.L. / Parker, M.W. / Cappai, R.
CitationJournal: J.Biol.Chem. / Year: 2003
Title: Structure of the Alzheimer's Disease Amyloid Precursor Protein Copper Binding Domain. A REGULATOR OF NEURONAL COPPER HOMEOSTASIS.
Authors: Barnham, K.J. / McKinstry, W.J. / Multhaup, G. / Galatis, D. / Morton, C.J. / Curtain, C.C. / Williamson, N.A. / White, A.R. / Hinds, M.G. / Norton, R.S. / Beyreuther, K. / Masters, C.L. / ...Authors: Barnham, K.J. / McKinstry, W.J. / Multhaup, G. / Galatis, D. / Morton, C.J. / Curtain, C.C. / Williamson, N.A. / White, A.R. / Hinds, M.G. / Norton, R.S. / Beyreuther, K. / Masters, C.L. / Parker, M.W. / Cappai, R.
History
DepositionMar 30, 2003Deposition site: RCSB / Processing site: PDBJ
Revision 1.0May 13, 2003Provider: repository / Type: Initial release
Revision 1.1Apr 29, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Feb 23, 2022Group: Database references / Derived calculations
Category: database_2 / pdbx_struct_assembly / pdbx_struct_oper_list
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.4Oct 30, 2024Group: Data collection / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / pdbx_entry_details / pdbx_modification_feature

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Amyloid beta A4 protein


Theoretical massNumber of molelcules
Total (without water)7,5891
Polymers7,5891
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
NMR ensembles
DataCriteria
Number of conformers (submitted / calculated)21 / 200structures with acceptable covalent geometry,structures with the lowest energy
Representative

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Components

#1: Protein Amyloid beta A4 protein / Amyloid Precursor Protein


Mass: 7588.806 Da / Num. of mol.: 1 / Fragment: Copper binding domain
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: APP / Plasmid: pIC9 / Production host: Pichia pastoris (fungus) / Strain (production host): GS115 / References: UniProt: P05067
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: SOLUTION NMR
NMR experiment
Conditions-IDExperiment-IDSolution-IDType
1113D 13C-separated NOESY
1213D 15N-separated NOESY

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Sample preparation

DetailsContents: 0.5mM CuBD U-15N,13C; 20mM phosphate buffer / Solvent system: 90% H2O, 10% D20
Sample conditionsIonic strength: 0.3 / pH: 6.9 / Pressure: 1 atm / Temperature: 303 K
Crystal grow
*PLUS
Method: other / Details: NMR

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NMR measurement

RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M
Radiation wavelengthRelative weight: 1
NMR spectrometerType: Bruker DPX / Manufacturer: Bruker / Model: DPX / Field strength: 600 MHz

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Processing

NMR software
NameVersionDeveloperClassification
CNS1Brungerstructure solution
CNS1refinement
RefinementMethod: distance geometry, simulated annealing / Software ordinal: 1 / Details: 1233 NOE restraints, 111 angle restraints
NMR ensembleConformer selection criteria: structures with acceptable covalent geometry,structures with the lowest energy
Conformers calculated total number: 200 / Conformers submitted total number: 21

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