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Yorodumi- PDB-4cqe: B-Raf Kinase V600E mutant in complex with a diarylthiazole B-Raf ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4cqe | ||||||
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Title | B-Raf Kinase V600E mutant in complex with a diarylthiazole B-Raf Inhibitor | ||||||
Components | SLC45A3-BRAF FUSION PROTEIN | ||||||
Keywords | TRANSFERASE / INHIBITOR COMPLEX | ||||||
Function / homology | Function and homology information CD4-positive, alpha-beta T cell differentiation / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative regulation of synaptic vesicle exocytosis / Signalling to p38 via RIT and RIN / head morphogenesis / 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 ...CD4-positive, alpha-beta T cell differentiation / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative regulation of synaptic vesicle exocytosis / Signalling to p38 via RIT and RIN / head morphogenesis / 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 / MAP kinase kinase kinase activity / 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 / negative regulation of endothelial cell apoptotic process / positive regulation of substrate adhesion-dependent cell spreading / positive regulation of stress fiber assembly / response to cAMP / cellular response to calcium ion / ERK1 and ERK2 cascade / substrate adhesion-dependent cell spreading / cellular response to nerve growth factor stimulus / thymus development / epidermal growth factor receptor signaling pathway / long-term synaptic potentiation / animal organ morphogenesis / RAF activation / Spry regulation of FGF signaling / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / visual learning / response to peptide hormone / cellular response to xenobiotic stimulus / 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 / positive regulation of peptidyl-serine phosphorylation / MAPK cascade / Signaling by BRAF and RAF1 fusions / presynapse / T cell receptor signaling pathway / regulation of cell population proliferation / cell body / T cell differentiation in thymus / scaffold protein binding / negative regulation of neuron apoptotic process / positive regulation of ERK1 and ERK2 cascade / non-specific serine/threonine protein kinase / protein kinase activity / neuron projection / protein phosphorylation / intracellular membrane-bounded organelle / protein serine kinase activity / protein serine/threonine kinase activity / calcium ion binding / positive regulation of gene expression / negative regulation of apoptotic process / protein-containing complex binding / 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: 2.3 Å | ||||||
Authors | Casale, E. / Fasolini, M. / Pulici, M. / Traquandi, G. / Marchionni, C. / Modugno, M. / Lupi, R. / Amboldi, N. / Colombo, N. / Corti, L. ...Casale, E. / Fasolini, M. / Pulici, M. / Traquandi, G. / Marchionni, C. / Modugno, M. / Lupi, R. / Amboldi, N. / Colombo, N. / Corti, L. / Gasparri, F. / Pastori, W. / Scolaro, A. / Donati, D. / Felder, E. / Galvani, A. / Isacchi, A. / Pesenti, E. / Ciomei, M. | ||||||
Citation | Journal: Chemmedchem / Year: 2015 Title: Optimization of Diarylthiazole B-Raf Inhibitors: Identification of a Compound Endowed with High Oral Antitumor Activity, Mitigated Herg Inhibition, and Low Paradoxical Effect. Authors: Pulici, M. / Traquandi, G. / Marchionni, C. / Modugno, M. / Lupi, R. / Amboldi, N. / Casale, E. / Colombo, N. / Corti, L. / Fasolini, M. / Gasparri, F. / Pastori, W. / Scolaro, A. / Donati, ...Authors: Pulici, M. / Traquandi, G. / Marchionni, C. / Modugno, M. / Lupi, R. / Amboldi, N. / Casale, E. / Colombo, N. / Corti, L. / Fasolini, M. / Gasparri, F. / Pastori, W. / Scolaro, A. / Donati, D. / Felder, E. / Galvani, A. / Isacchi, A. / Pesenti, E. / Ciomei, M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4cqe.cif.gz | 116.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4cqe.ent.gz | 89.9 KB | Display | PDB format |
PDBx/mmJSON format | 4cqe.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4cqe_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 4cqe_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 4cqe_validation.xml.gz | 22.6 KB | Display | |
Data in CIF | 4cqe_validation.cif.gz | 29.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cq/4cqe ftp://data.pdbj.org/pub/pdb/validation_reports/cq/4cqe | HTTPS FTP |
-Related structure data
Related structure data | 3c4cS S: Starting model for refinement |
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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: 31613.238 Da / Num. of mol.: 2 / Fragment: KINASE DOMAIN, RESIDUES 11-286 / Mutation: YES Source method: isolated from a genetically manipulated source Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: D7PBN4, UniProt: P15056*PLUS #2: Chemical | #3: Water | ChemComp-HOH / | Sequence details | RESIDUES G446 P447 ARE EXPRESSION TAG RESIDUES I543A I544S I551K Q562R L588N V600E K630S F667E ...RESIDUES G446 P447 ARE EXPRESSION | |
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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: 2.63 Å3/Da / Density % sol: 52.9 % / Description: NONE |
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Crystal grow | Method: vapor diffusion, sitting drop Details: 0.1M HEPES PH 7.5.0, 0.2 M MGCL2 AND 20% PEG6000, VAPOR DIFFUSION, SITTING DROP |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID29 / Wavelength: 0.98 |
Detector | Type: ADSC CCD / Detector: CCD / Date: Feb 1, 2011 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.98 Å / Relative weight: 1 |
Reflection | Resolution: 2.3→40 Å / Num. obs: 28170 / % possible obs: 99.8 % / Observed criterion σ(I): 0 / Redundancy: 6.1 % / Rmerge(I) obs: 0.08 / Net I/σ(I): 15.2 |
Reflection shell | Resolution: 2.3→2.3 Å / Rmerge(I) obs: 0.35 / % possible all: 96.1 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 3C4C Resolution: 2.3→30 Å / Cor.coef. Fo:Fc: 0.952 / Cor.coef. Fo:Fc free: 0.928 / SU B: 6.984 / SU ML: 0.17 / Cross valid method: THROUGHOUT / ESU R: 0.314 / ESU R Free: 0.236 / Stereochemistry target values: MAXIMUM LIKELIHOOD / 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 / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 51.359 Å2
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Refinement step | Cycle: LAST / Resolution: 2.3→30 Å
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