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Yorodumi- PDB-5f95: Crystal structure of GSK3b in complex with Compound 18: 2-[(cyclo... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5f95 | ||||||
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Title | Crystal structure of GSK3b in complex with Compound 18: 2-[(cyclopropylcarbonyl)amino]-N-(4-phenylpyridin-3-yl)pyridine-4-carboxamide | ||||||
Components | Glycogen synthase kinase-3 beta | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / GSK3b / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
Function / homology | Function and homology information negative regulation of glycogen (starch) synthase activity / neuron projection organization / regulation of microtubule anchoring at centrosome / negative regulation of mesenchymal stem cell differentiation / beta-catenin destruction complex disassembly / negative regulation of type B pancreatic cell development / superior temporal gyrus development / positive regulation of protein localization to cilium / negative regulation of glycogen biosynthetic process / negative regulation of dopaminergic neuron differentiation ...negative regulation of glycogen (starch) synthase activity / neuron projection organization / regulation of microtubule anchoring at centrosome / negative regulation of mesenchymal stem cell differentiation / beta-catenin destruction complex disassembly / negative regulation of type B pancreatic cell development / superior temporal gyrus development / positive regulation of protein localization to cilium / negative regulation of glycogen biosynthetic process / negative regulation of dopaminergic neuron differentiation / maintenance of cell polarity / positive regulation of protein localization to centrosome / : / positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / positive regulation of cilium assembly / negative regulation of protein acetylation / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / beta-catenin destruction complex / tau-protein kinase / regulation of microtubule-based process / CRMPs in Sema3A signaling / regulation of protein export from nucleus / heart valve development / Beta-catenin phosphorylation cascade / Signaling by GSK3beta mutants / CTNNB1 S33 mutants aren't phosphorylated / CTNNB1 S37 mutants aren't phosphorylated / CTNNB1 S45 mutants aren't phosphorylated / CTNNB1 T41 mutants aren't phosphorylated / Maturation of nucleoprotein / cellular response to interleukin-3 / regulation of axon extension / Wnt signalosome / regulation of long-term synaptic potentiation / negative regulation of protein localization to nucleus / Disassembly of the destruction complex and recruitment of AXIN to the membrane / Maturation of nucleoprotein / AKT phosphorylates targets in the cytosol / positive regulation of cell-matrix adhesion / negative regulation of calcineurin-NFAT signaling cascade / dopamine receptor signaling pathway / regulation of dendrite morphogenesis / negative regulation of phosphoprotein phosphatase activity / regulation of axonogenesis / establishment of cell polarity / tau-protein kinase activity / glycogen metabolic process / ER overload response / regulation of neuron projection development / Constitutive Signaling by AKT1 E17K in Cancer / dynactin binding / protein kinase A catalytic subunit binding / NF-kappaB binding / canonical Wnt signaling pathway / Regulation of HSF1-mediated heat shock response / epithelial to mesenchymal transition / negative regulation of osteoblast differentiation / negative regulation of protein-containing complex assembly / regulation of microtubule cytoskeleton organization / positive regulation of autophagy / regulation of cellular response to heat / cellular response to retinoic acid / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / extrinsic apoptotic signaling pathway / extrinsic apoptotic signaling pathway in absence of ligand / excitatory postsynaptic potential / presynaptic modulation of chemical synaptic transmission / positive regulation of protein export from nucleus / positive regulation of protein ubiquitination / Ubiquitin-dependent degradation of Cyclin D / hippocampus development / positive regulation of protein-containing complex assembly / positive regulation of cell differentiation / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / peptidyl-threonine phosphorylation / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / negative regulation of canonical Wnt signaling pathway / tau protein binding / Degradation of beta-catenin by the destruction complex / B-WICH complex positively regulates rRNA expression / regulation of circadian rhythm / beta-catenin binding / positive regulation of GTPase activity / circadian rhythm / neuron projection development / cellular response to amyloid-beta / positive regulation of protein catabolic process / Regulation of RUNX2 expression and activity / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / p53 binding / presynapse / insulin receptor signaling pathway / positive regulation of protein binding / kinase activity / postsynapse / proteasome-mediated ubiquitin-dependent protein catabolic process / peptidyl-serine phosphorylation Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / Resolution: 2.525 Å | ||||||
Authors | Lewis, H.A. / Kish, K. / Luo, G. / Dubowchick, G.M. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2016 Title: Discovery of Isonicotinamides as Highly Selective, Brain Penetrable, and Orally Active Glycogen Synthase Kinase-3 Inhibitors. Authors: Luo, G. / Chen, L. / Burton, C.R. / Xiao, H. / Sivaprakasam, P. / Krause, C.M. / Cao, Y. / Liu, N. / Lippy, J. / Clarke, W.J. / Snow, K. / Raybon, J. / Arora, V. / Pokross, M. / Kish, K. / ...Authors: Luo, G. / Chen, L. / Burton, C.R. / Xiao, H. / Sivaprakasam, P. / Krause, C.M. / Cao, Y. / Liu, N. / Lippy, J. / Clarke, W.J. / Snow, K. / Raybon, J. / Arora, V. / Pokross, M. / Kish, K. / Lewis, H.A. / Langley, D.R. / Macor, J.E. / Dubowchik, G.M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5f95.cif.gz | 270.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5f95.ent.gz | 218.3 KB | Display | PDB format |
PDBx/mmJSON format | 5f95.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/f9/5f95 ftp://data.pdbj.org/pub/pdb/validation_reports/f9/5f95 | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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Unit cell |
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-Components
#1: Protein | Mass: 39843.848 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GSK3B / Production host: unidentified baculovirus References: UniProt: P49841, tau-protein kinase, non-specific serine/threonine protein kinase #2: Chemical | #3: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION |
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-Sample preparation
Crystal | Density Matthews: 3.76 Å3/Da / Density % sol: 67.27 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion Details: Crystals grown in the presence of 25% PEG 1500 and 0.1 M MMT pH 4.0 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Apr 6, 2011 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.5→30.3 Å / Num. obs: 40511 / % possible obs: 99.8 % / Redundancy: 5.9 % / Net I/σ(I): 10.4 |
-Processing
Software |
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Refinement | Resolution: 2.525→30.274 Å / SU ML: 0.37 / Cross valid method: FREE R-VALUE / σ(F): 1.9 / Phase error: 28.76 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.525→30.274 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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