+Open data
-Basic information
Entry | Database: PDB / ID: 4mnf | ||||||
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Title | Crystal structure of BRAF-V600E bound to GDC0879 | ||||||
Components | Serine/threonine-protein kinase B-raf | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / RAF / MAPK / kinase domain / ATP-binding / ERK / RAS / PAK / active conformation / TRANSFERASE-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: 2.802 Å | ||||||
Authors | Sudhamsu, J. / Haling, J.R. / Morales, T. / Brandhuber, B. / Hymowitz, S.G. | ||||||
Citation | Journal: Cancer Cell / Year: 2014 Title: Structure of the BRAF-MEK Complex Reveals a Kinase Activity Independent Role for BRAF in MAPK Signaling. Authors: Haling, J.R. / Sudhamsu, J. / Yen, I. / Sideris, S. / Sandoval, W. / Phung, W. / Bravo, B.J. / Giannetti, A.M. / Peck, A. / Masselot, A. / Morales, T. / Smith, D. / Brandhuber, B.J. / Hymowitz, S.G. / Malek, S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4mnf.cif.gz | 121.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4mnf.ent.gz | 93.1 KB | Display | PDB format |
PDBx/mmJSON format | 4mnf.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4mnf_validation.pdf.gz | 989.7 KB | Display | wwPDB validaton report |
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Full document | 4mnf_full_validation.pdf.gz | 995.3 KB | Display | |
Data in XML | 4mnf_validation.xml.gz | 21.8 KB | Display | |
Data in CIF | 4mnf_validation.cif.gz | 29.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mn/4mnf ftp://data.pdbj.org/pub/pdb/validation_reports/mn/4mnf | HTTPS FTP |
-Related structure data
Related structure data | 4mneC 3q4cS C: citing same article (ref.) S: Starting model for refinement |
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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: 37290.914 Da / Num. of mol.: 2 / Fragment: kinase domain (UNP residues 432-736) / Mutation: V600E Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BRAF, BRAF1, RAFB1 / Production host: Trichoplusia ni (cabbage looper) References: UniProt: P15056, non-specific serine/threonine protein kinase #2: Chemical | #3: Chemical | ChemComp-CL / | #4: 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: 2.65 Å3/Da / Density % sol: 53.61 % |
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Crystal grow | Temperature: 292 K / Method: vapor diffusion, sitting drop / pH: 7.5 Details: 10% PEG8000, 0.1 M HEPES, pH 7.5, 0.5 M sodium chloride, VAPOR DIFFUSION, SITTING DROP, temperature 292K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SSRL / Beamline: BL11-1 / Wavelength: 0.98 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Oct 26, 2011 |
Radiation | Monochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.98 Å / Relative weight: 1 |
Reflection | Resolution: 2.802→49.87 Å / Num. all: 20427 / Num. obs: 20427 / % possible obs: 99.8 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 5.1 % / Rsym value: 0.093 / Net I/σ(I): 16.7 |
Reflection shell | Resolution: 2.802→2.9 Å / Redundancy: 5.2 % / Mean I/σ(I) obs: 2.7 / Rsym value: 0.643 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 3Q4C Resolution: 2.802→49.87 Å / SU ML: 0.43 / σ(F): 1.35 / σ(I): 2.7 / Phase error: 28.87 / 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.802→49.87 Å
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Refine LS restraints |
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LS refinement shell |
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