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Yorodumi- PDB-7ofv: NMR-guided design of potent and selective EphA4 agonistic ligands -
+Open data
-Basic information
Entry | Database: PDB / ID: 7ofv | ||||||
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Title | NMR-guided design of potent and selective EphA4 agonistic ligands | ||||||
Components |
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Keywords | TRANSFERASE / EphA4 / 150D4 / ephrin / RTK | ||||||
Function / homology | Function and homology information DH domain binding / neuron projection fasciculation / positive regulation of Rho guanyl-nucleotide exchange factor activity / corticospinal tract morphogenesis / regulation of astrocyte differentiation / negative regulation of proteolysis involved in protein catabolic process / neuron projection guidance / nephric duct morphogenesis / regulation of synapse pruning / fasciculation of sensory neuron axon ...DH domain binding / neuron projection fasciculation / positive regulation of Rho guanyl-nucleotide exchange factor activity / corticospinal tract morphogenesis / regulation of astrocyte differentiation / negative regulation of proteolysis involved in protein catabolic process / neuron projection guidance / nephric duct morphogenesis / regulation of synapse pruning / fasciculation of sensory neuron axon / fasciculation of motor neuron axon / synapse pruning / negative regulation of cellular response to hypoxia / negative regulation of axon regeneration / positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process / glial cell migration / transmembrane-ephrin receptor activity / PH domain binding / GPI-linked ephrin receptor activity / regulation of modification of synaptic structure / negative regulation of epithelial to mesenchymal transition / regulation of dendritic spine morphogenesis / negative regulation of cell adhesion / motor neuron axon guidance / adult walking behavior / adherens junction organization / positive regulation of dendrite morphogenesis / EPH-Ephrin signaling / Somitogenesis / regulation of axonogenesis / positive regulation of amyloid-beta formation / cochlea development / regulation of GTPase activity / EPHA-mediated growth cone collapse / negative regulation of long-term synaptic potentiation / positive regulation of cell adhesion / EPH-ephrin mediated repulsion of cells / ephrin receptor signaling pathway / positive regulation of protein tyrosine kinase activity / axon terminus / axonal growth cone / protein tyrosine kinase binding / ephrin receptor binding / negative regulation of cell migration / dendritic shaft / filopodium / axon guidance / postsynaptic density membrane / adherens junction / Schaffer collateral - CA1 synapse / neuromuscular junction / negative regulation of ERK1 and ERK2 cascade / receptor protein-tyrosine kinase / peptidyl-tyrosine phosphorylation / cellular response to amyloid-beta / negative regulation of neuron projection development / presynaptic membrane / amyloid-beta binding / kinase activity / perikaryon / early endosome membrane / protein tyrosine kinase activity / mitochondrial outer membrane / dendritic spine / protein autophosphorylation / negative regulation of translation / protein stabilization / cell adhesion / protein kinase activity / positive regulation of cell migration / axon / glutamatergic synapse / dendrite / positive regulation of cell population proliferation / cell surface / ATP binding / identical protein binding / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) synthetic construct (others) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.43 Å | ||||||
Authors | Ganichkin, O.M. / Craig, T.K. / Baggio, C. / Pellecchia, M. | ||||||
Funding support | United States, 1items
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Citation | Journal: J.Med.Chem. / Year: 2021 Title: NMR-Guided Design of Potent and Selective EphA4 Agonistic Ligands. Authors: Baggio, C. / Kulinich, A. / Dennys, C.N. / Rodrigo, R. / Meyer, K. / Ethell, I. / Pellecchia, M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7ofv.cif.gz | 106.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7ofv.ent.gz | 75.6 KB | Display | PDB format |
PDBx/mmJSON format | 7ofv.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/of/7ofv ftp://data.pdbj.org/pub/pdb/validation_reports/of/7ofv | HTTPS FTP |
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-Related structure data
Related structure data | 5jr2S 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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Unit cell |
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-Components
#1: Protein | Mass: 21259.100 Da / Num. of mol.: 1 / Mutation: C204A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EPHA4, HEK8, SEK, TYRO1 / Production host: Escherichia coli (E. coli) References: UniProt: P54764, receptor protein-tyrosine kinase |
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#2: Protein/peptide | Mass: 957.152 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
#3: Chemical | ChemComp-ACT / |
#4: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.47 Å3/Da / Density % sol: 50.11 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 4.5 Details: 0.10 M Na Acet, pH 4.50, 1.20 M K2HPO4, 0.80 M NaH2PO4 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: PETRA III, EMBL c/o DESY / Beamline: P13 (MX1) / Wavelength: 1.0332 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Aug 20, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.0332 Å / Relative weight: 1 |
Reflection | Resolution: 1.43→51.552 Å / Num. obs: 34710 / % possible obs: 93.8 % / Redundancy: 12.9 % / CC1/2: 1 / Rmerge(I) obs: 0.053 / Rpim(I) all: 0.015 / Rrim(I) all: 0.055 / Rsym value: 0.053 / Net I/σ(I): 24.9 |
Reflection shell | Resolution: 1.43→1.544 Å / Redundancy: 4 % / Rmerge(I) obs: 0.883 / Mean I/σ(I) obs: 1.2 / Num. unique obs: 1736 / CC1/2: 0.534 / Rpim(I) all: 0.48 / Rrim(I) all: 1.012 / Rsym value: 0.883 / % possible all: 57.1 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5JR2 Resolution: 1.43→51.547 Å / Cor.coef. Fo:Fc: 0.972 / Cor.coef. Fo:Fc free: 0.951 / SU B: 3.147 / SU ML: 0.051 / Cross valid method: FREE R-VALUE / ESU R: 0.079 / ESU R Free: 0.077 Details: Hydrogens have been added in their 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 BULK SOLVENT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 20.129 Å2
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Refinement step | Cycle: LAST / Resolution: 1.43→51.547 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: 20
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