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Yorodumi- PDB-6hk3: Crystal structure of GSK-3B in complex with pyrazine inhibitor C44 -
+Open data
-Basic information
Entry | Database: PDB / ID: 6hk3 | ||||||
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Title | Crystal structure of GSK-3B in complex with pyrazine inhibitor C44 | ||||||
Components |
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Keywords | TRANSFERASE / GSK 3B / Complex / pyrazine / inhibitor | ||||||
Function / homology | Function and homology information regulation of microtubule anchoring at centrosome / negative regulation of glycogen (starch) synthase activity / neuron projection organization / 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 ...regulation of microtubule anchoring at centrosome / negative regulation of glycogen (starch) synthase activity / neuron projection organization / 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 / CRMPs in Sema3A signaling / heart valve development / regulation of microtubule-based process / regulation of protein export from nucleus / 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 / Wnt signalosome / negative regulation of protein localization to nucleus / negative regulation of TOR signaling / regulation of long-term synaptic potentiation / Disassembly of the destruction complex and recruitment of AXIN to the membrane / Maturation of nucleoprotein / AKT phosphorylates targets in the cytosol / negative regulation of calcineurin-NFAT signaling cascade / positive regulation of cell-matrix adhesion / regulation of axon extension / G protein-coupled dopamine receptor signaling pathway / negative regulation of phosphoprotein phosphatase activity / regulation of dendrite morphogenesis / establishment of cell polarity / regulation of axonogenesis / tau-protein kinase activity / glycogen metabolic process / ER overload response / Constitutive Signaling by AKT1 E17K in Cancer / protein kinase A catalytic subunit binding / dynactin binding / NF-kappaB binding / Regulation of HSF1-mediated heat shock response / epithelial to mesenchymal transition / negative regulation of osteoblast differentiation / canonical Wnt signaling pathway / negative regulation of protein-containing complex assembly / positive regulation of autophagy / regulation of microtubule cytoskeleton organization / 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 / presynaptic modulation of chemical synaptic transmission / negative regulation of insulin receptor signaling pathway / excitatory postsynaptic potential / positive regulation of protein export from nucleus / positive regulation of GTPase activity / positive regulation of protein ubiquitination / Ubiquitin-dependent degradation of Cyclin D / hippocampus development / 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 / positive regulation of protein-containing complex assembly / Degradation of beta-catenin by the destruction complex / negative regulation of canonical Wnt signaling pathway / tau protein binding / B-WICH complex positively regulates rRNA expression / regulation of circadian rhythm / beta-catenin binding / circadian rhythm / positive regulation of protein catabolic process / cellular response to amyloid-beta / Regulation of RUNX2 expression and activity / neuron projection development / positive regulation of neuron apoptotic process / p53 binding / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / presynapse / positive regulation of protein binding / insulin receptor signaling pathway / negative regulation of neuron projection development / kinase activity Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.35 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 | 6hk3.cif.gz | 161.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6hk3.ent.gz | 126.1 KB | Display | PDB format |
PDBx/mmJSON format | 6hk3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6hk3_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 6hk3_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 6hk3_validation.xml.gz | 31.1 KB | Display | |
Data in CIF | 6hk3_validation.cif.gz | 42.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/hk/6hk3 ftp://data.pdbj.org/pub/pdb/validation_reports/hk/6hk3 | HTTPS FTP |
-Related structure data
Related structure data | 6hk4C 6hk7C 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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2 |
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Unit cell |
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-Components
-Protein / Protein/peptide , 2 types, 3 molecules ABN
#1: Protein | Mass: 39882.773 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GSK3B / Production host: Trichoplusia ni (cabbage looper) References: UniProt: P49841, tau-protein kinase, non-specific serine/threonine protein kinase #2: Protein/peptide | | Mass: 909.931 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Trichoplusia ni (cabbage looper) |
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-Non-polymers , 6 types, 200 molecules
#3: Chemical | #4: Chemical | #5: Chemical | ChemComp-GOL / #6: Chemical | #7: Chemical | #8: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.44 Å3/Da / Density % sol: 64.21 % |
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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: Mar 20, 2018 | ||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
Reflection | Resolution: 2.3→46.22 Å / Num. obs: 46585 / % possible obs: 97.1 % / Redundancy: 2.4 % / CC1/2: 0.994 / Rmerge(I) obs: 0.098 / Rpim(I) all: 0.077 / Rrim(I) all: 0.125 / Net I/σ(I): 5.2 / Num. measured all: 113743 / Scaling rejects: 2 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4ACD Resolution: 2.35→42.977 Å / SU ML: 0.35 / Cross valid method: THROUGHOUT / σ(F): 1.96 / Phase error: 26.45 / 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 | ||||||||||||||||||||||||
Displacement parameters | Biso max: 136.69 Å2 / Biso mean: 56.4885 Å2 / Biso min: 18.99 Å2 | ||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.35→42.977 Å
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