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Yorodumi- PDB-6hk7: Crystal structure of GSK-3B in complex with pyrazine inhibitor C50 -
+Open data
-Basic information
Entry | Database: PDB / ID: 6hk7 | ||||||
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Title | Crystal structure of GSK-3B in complex with pyrazine inhibitor C50 | ||||||
Components | Glycogen synthase kinase-3 beta | ||||||
Keywords | TRANSFERASE / GSK 3B / Complex / pyrazine / inhibitor | ||||||
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 / MOLECULAR REPLACEMENT / Resolution: 3.2 Å | ||||||
Authors | Piretti, V. / Giabbai, B. / Demitri, N. / Di Martino, R. / Tripathi, S.K. / Gobbo, D. / Decherchi, S. / Storici, P. / Girotto, S. / Cavalli, A. | ||||||
Citation | Journal: J Chem Theory Comput / Year: 2019 Title: Investigating Drug-Target Residence Time in Kinases through Enhanced Sampling Simulations. Authors: Gobbo, D. / Piretti, V. / Di Martino, R.M.C. / Tripathi, S.K. / Giabbai, B. / Storici, P. / Demitri, N. / Girotto, S. / Decherchi, S. / Cavalli, A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6hk7.cif.gz | 153.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6hk7.ent.gz | 118.4 KB | Display | PDB format |
PDBx/mmJSON format | 6hk7.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/hk/6hk7 ftp://data.pdbj.org/pub/pdb/validation_reports/hk/6hk7 | HTTPS FTP |
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-Related structure data
Related structure data | 6hk3C 6hk4C 4acdS S: Starting model for refinement 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: 39525.344 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GSK3B / Production host: Baculovirus expression vector pFastBac1-HM References: UniProt: P49841, tau-protein kinase, non-specific serine/threonine protein kinase |
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#2: Chemical | ChemComp-GOL / |
#3: Chemical | ChemComp-DMS / |
#4: Chemical | ChemComp-G8N / |
#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: 3.07 Å3/Da / Density % sol: 59.96 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7.4 / Details: 0.2M potassium fluoride 22% PEG 3350 |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: ELETTRA / Beamline: 5.2R / Wavelength: 1 Å | ||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 2M / Detector: PIXEL / Date: May 17, 2018 | ||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | ||||||||||||||||||||||||
Reflection | Resolution: 3→51.86 Å / Num. obs: 10015 / % possible obs: 99.5 % / Redundancy: 5.4 % / CC1/2: 0.973 / Rmerge(I) obs: 0.281 / Rpim(I) all: 0.133 / Rrim(I) all: 0.312 / Net I/σ(I): 4.9 / Num. measured all: 53759 / Scaling rejects: 19 | ||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4ACD Resolution: 3.2→46.87 Å / Cor.coef. Fo:Fc: 0.919 / Cor.coef. Fo:Fc free: 0.853 / SU B: 65.595 / SU ML: 0.481 / Cross valid method: THROUGHOUT / ESU R Free: 0.541 / 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 47.85 Å2
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Refinement step | Cycle: 1 / Resolution: 3.2→46.87 Å
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