+Open data
-Basic information
Entry | Database: PDB / ID: 4xv1 | ||||||
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Title | B-Raf Kinase V600E oncogenic mutant in complex with PLX7904 | ||||||
Components | Serine/threonine-protein kinase B-raf | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / B-RAF / BRAF / PROTO-ONCOGENE / V600E / KINASE / TRANSFERASE / TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX | ||||||
Function / homology | Function and homology information CD4-positive, alpha-beta T cell differentiation / trehalose metabolism in response to stress / 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 ...CD4-positive, alpha-beta T cell differentiation / trehalose metabolism in response to stress / 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 / cellular response to calcium ion / ERK1 and ERK2 cascade / 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 / positive regulation of peptidyl-serine phosphorylation / T cell differentiation in thymus / T cell receptor signaling pathway / regulation of cell population proliferation / cell body / scaffold protein binding / negative regulation of neuron apoptotic process / Ras protein signal transduction / 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 / 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: 2.47 Å | ||||||
Authors | Zhang, Y. / Zhang, C. | ||||||
Citation | Journal: Nature / Year: 2015 Title: RAF inhibitors that evade paradoxical MAPK pathway activation. Authors: Zhang, C. / Spevak, W. / Zhang, Y. / Burton, E.A. / Ma, Y. / Habets, G. / Zhang, J. / Lin, J. / Ewing, T. / Matusow, B. / Tsang, G. / Marimuthu, A. / Cho, H. / Wu, G. / Wang, W. / Fong, D. / ...Authors: Zhang, C. / Spevak, W. / Zhang, Y. / Burton, E.A. / Ma, Y. / Habets, G. / Zhang, J. / Lin, J. / Ewing, T. / Matusow, B. / Tsang, G. / Marimuthu, A. / Cho, H. / Wu, G. / Wang, W. / Fong, D. / Nguyen, H. / Shi, S. / Womack, P. / Nespi, M. / Shellooe, R. / Carias, H. / Powell, B. / Light, E. / Sanftner, L. / Walters, J. / Tsai, J. / West, B.L. / Visor, G. / Rezaei, H. / Lin, P.S. / Nolop, K. / Ibrahim, P.N. / Hirth, P. / Bollag, G. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4xv1.cif.gz | 216.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4xv1.ent.gz | 173.5 KB | Display | PDB format |
PDBx/mmJSON format | 4xv1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xv/4xv1 ftp://data.pdbj.org/pub/pdb/validation_reports/xv/4xv1 | HTTPS FTP |
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-Related structure data
Related structure data | 4xv2C 4xv3C 4xv9C 4k0i 4k16 4k1a 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: 33293.133 Da / Num. of mol.: 2 / Fragment: UNP RESIDUES 444-705 Mutation: S446A,S447A,I543A,I544S,I551K,Q562R,L588N,V600E,K630S,F667E,Y673S,A688R Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BRAF, BRAF1, RAFB1 / Production host: Escherichia coli (E. coli) References: UniProt: P15056, non-specific serine/threonine protein kinase #2: Chemical | ChemComp-904 / | #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: 2.23 Å3/Da / Density % sol: 44.76 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 6 Details: 100MM BISTRIS AT PH 6.0, 12.5% 2,5- HEXANEDIOL, 12% PEG3350, VAPOR DIFFUSION, SITTING DROP, TEMPERATURE 277K PH range: 6 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 8.3.1 / Wavelength: 1.11587 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Apr 14, 2012 |
Radiation | Monochromator: KHOZU DOUBLE FLAT CRYSTAL / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.11587 Å / Relative weight: 1 |
Reflection | Resolution: 2.47→75.958 Å / Num. obs: 22008 / % possible obs: 99.9 % / Observed criterion σ(I): -3 / Redundancy: 5.8 % / Net I/σ(I): 7.8 |
Reflection shell | Resolution: 2.47→2.6 Å / Redundancy: 5.9 % / Rmerge(I) obs: 0.903 / Mean I/σ(I) obs: 1 / Rsym value: 0.899 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.47→75.958 Å / SU ML: 0.42 / Cross valid method: FREE R-VALUE / σ(F): 1.38 / Phase error: 27.2 / Stereochemistry target values: ENGH & HUBER
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Solvent computation | Shrinkage radii: 0.98 Å / VDW probe radii: 1.2 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 55.83 Å2 / ksol: 0.35 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters |
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Refinement step | Cycle: LAST / Resolution: 2.47→75.958 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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