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Yorodumi- PDB-6b8u: Crystals Structure of B-Raf kinase domain in complex with an Imid... -
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-Basic information
Entry | Database: PDB / ID: 6b8u | ||||||
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Title | Crystals Structure of B-Raf kinase domain in complex with an Imidazopyridinyl benzamide inhibitor | ||||||
Components | Serine/threonine-protein kinase B-raf | ||||||
Keywords | Transferase/Transferase Inhibitor / Proto-oncogene B-Raf / p94 / v-Raf murine sarcoma viral oncogene homolog B1 / ONCOPROTEIN / Transferase-Transferase Inhibitor complex | ||||||
Function / homology | Function and homology information trehalose metabolism in response to stress / CD4-positive, alpha-beta T cell differentiation / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative regulation of synaptic vesicle exocytosis / head morphogenesis / Signalling to p38 via RIT and RIN / myeloid progenitor cell differentiation / ARMS-mediated activation / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling ...trehalose metabolism in response to stress / CD4-positive, alpha-beta T cell differentiation / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative regulation of synaptic vesicle exocytosis / head morphogenesis / Signalling to p38 via RIT and RIN / myeloid progenitor cell differentiation / ARMS-mediated activation / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / endothelial cell apoptotic process / negative regulation of fibroblast migration / positive regulation of glucose transmembrane transport / establishment of protein localization to membrane / mitogen-activated protein kinase kinase binding / regulation of T cell differentiation / Negative feedback regulation of MAPK pathway / positive regulation of axonogenesis / Frs2-mediated activation / stress fiber assembly / positive regulation of axon regeneration / face development / synaptic vesicle exocytosis / somatic stem cell population maintenance / MAP kinase kinase activity / thyroid gland development / MAP kinase kinase kinase activity / negative regulation of endothelial cell apoptotic process / positive regulation of substrate adhesion-dependent cell spreading / positive regulation of stress fiber assembly / response to cAMP / ERK1 and ERK2 cascade / cellular response to calcium ion / substrate adhesion-dependent cell spreading / cellular response to nerve growth factor stimulus / thymus development / long-term synaptic potentiation / animal organ morphogenesis / Spry regulation of FGF signaling / RAF activation / Signaling by high-kinase activity BRAF mutants / visual learning / MAP2K and MAPK activation / epidermal growth factor receptor signaling pathway / response to peptide hormone / Negative regulation of MAPK pathway / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / MAPK cascade / Signaling by BRAF and RAF1 fusions / cellular response to xenobiotic stimulus / presynapse / cell body / positive regulation of peptidyl-serine phosphorylation / T cell differentiation in thymus / regulation of cell population proliferation / T cell receptor signaling pathway / scaffold protein binding / negative regulation of neuron apoptotic process / positive regulation of ERK1 and ERK2 cascade / non-specific serine/threonine protein kinase / neuron projection / protein kinase activity / protein phosphorylation / protein serine kinase activity / intracellular membrane-bounded organelle / protein serine/threonine kinase activity / calcium ion binding / protein-containing complex binding / positive regulation of gene expression / negative regulation of apoptotic process / mitochondrion / ATP binding / identical protein binding / nucleus / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.68 Å | ||||||
Authors | Appleton, B.A. / Murray, J. / Shafer, C.M. | ||||||
Citation | Journal: Bioorg. Med. Chem. Lett. / Year: 2017 Title: Imidazo[1,2-a]pyridin-6-yl-benzamide analogs as potent RAF inhibitors. Authors: Smith, A. / Ni, Z.J. / Poon, D. / Huang, Z. / Chen, Z. / Zhang, Q. / Tandeske, L. / Merritt, H. / Shoemaker, K. / Chan, J. / Kaufman, S. / Huh, K. / Murray, J. / Appleton, B.A. / Cowan- ...Authors: Smith, A. / Ni, Z.J. / Poon, D. / Huang, Z. / Chen, Z. / Zhang, Q. / Tandeske, L. / Merritt, H. / Shoemaker, K. / Chan, J. / Kaufman, S. / Huh, K. / Murray, J. / Appleton, B.A. / Cowan-Jacob, S.W. / Scheufler, C. / Kanazawa, T. / Jansen, J.M. / Stuart, D. / Shafer, C.M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6b8u.cif.gz | 214.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6b8u.ent.gz | 170.1 KB | Display | PDB format |
PDBx/mmJSON format | 6b8u.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/b8/6b8u ftp://data.pdbj.org/pub/pdb/validation_reports/b8/6b8u | HTTPS FTP |
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-Related structure data
Related structure data | 5mz3C 2fb8S 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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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 31913.881 Da / Num. of mol.: 2 / Fragment: UNP residues 445-723 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BRAF, BRAF1, RAFB1 / Plasmid: pBlueBac4.5 / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): SF21 References: UniProt: P15056, non-specific serine/threonine protein kinase #2: Chemical | #3: 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: 2.82 Å3/Da / Density % sol: 56.38 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 4.7 Details: 10% PEG8000, 0.1 M sodium citrate pH 4.7, and 0.2 M sodium chloride |
-Data collection
Diffraction | Mean temperature: 100 K / Ambient temp details: LN2 |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 8.3.1 / Wavelength: 1.11589 Å |
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Jun 30, 2007 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.11589 Å / Relative weight: 1 |
Reflection | Resolution: 2.68→46.8 Å / Num. obs: 21143 / % possible obs: 100 % / Redundancy: 5.1 % / Biso Wilson estimate: 56.71 Å2 / Rmerge(I) obs: 0.152 / Rpim(I) all: 0.074 / Net I/σ(I): 11.4 |
Reflection shell | Resolution: 2.68→2.78 Å / Redundancy: 5.2 % / Rmerge(I) obs: 0.768 / Mean I/σ(I) obs: 2.7 / Num. unique obs: 2056 / Rpim(I) all: 0.369 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2FB8 Resolution: 2.68→46.75 Å / Cor.coef. Fo:Fc: 0.9378 / Cor.coef. Fo:Fc free: 0.9196 / SU R Cruickshank DPI: 0.452 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.49 / SU Rfree Blow DPI: 0.259 / SU Rfree Cruickshank DPI: 0.258
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Displacement parameters | Biso mean: 41.24 Å2
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Refine analyze | Luzzati coordinate error obs: 0.296 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Resolution: 2.68→46.75 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.68→2.81 Å / Total num. of bins used: 11
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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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