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Yorodumi- PDB-6nsq: Crystal structure of BRAF kinase domain bound to the inhibitor 2l -
+Open data
-Basic information
Entry | Database: PDB / ID: 6nsq | ||||||
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Title | Crystal structure of BRAF kinase domain bound to the inhibitor 2l | ||||||
Components | Serine/threonine-protein kinase B-raf | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / BRAF inhibitors / SIGNALING PROTEIN / TRANSFERASE-TRANSFERASE Inhibitor complex / TRANSFERASE | ||||||
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: 3.05 Å | ||||||
Authors | Maisonneuve, P. / Kurinov, I. / Assadieskandar, A. / Yu, C. / Zhang, C. / Sicheri, F. | ||||||
Citation | Journal: Acs Med.Chem.Lett. / Year: 2019 Title: Rigidification Dramatically Improves Inhibitor Selectivity for RAF Kinases. Authors: Assadieskandar, A. / Yu, C. / Maisonneuve, P. / Kurinov, I. / Sicheri, F. / Zhang, C. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6nsq.cif.gz | 264.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6nsq.ent.gz | 178.1 KB | Display | PDB format |
PDBx/mmJSON format | 6nsq.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ns/6nsq ftp://data.pdbj.org/pub/pdb/validation_reports/ns/6nsq | HTTPS FTP |
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-Related structure data
Related structure data | 4r5yS S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Ens-ID: 1
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-Components
#1: Protein | Mass: 32249.941 Da / Num. of mol.: 2 / Fragment: residues 444-723 Mutation: I543A, I544S, I551K, Q562R, L588N, K630S, F667E, Y673S, A688R, L706S, Q709R, S713E, L716E, S720E, P722S, K723G 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 | #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: 2.63 Å3/Da / Density % sol: 53.15 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7 Details: 25% PEG 3350, 0.1M Bis-Tris Propane pH 7.75, 0.2M Sodium Malonate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 24-ID-E / Wavelength: 0.97918 Å |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Apr 2, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97918 Å / Relative weight: 1 |
Reflection | Resolution: 3.05→62.54 Å / Num. obs: 12438 / % possible obs: 98.34 % / Redundancy: 2 % / Biso Wilson estimate: 76.96 Å2 / CC1/2: 0.996 / Rmerge(I) obs: 0.07208 / Rrim(I) all: 0.1019 / Net I/σ(I): 6.11 |
Reflection shell | Resolution: 3.05→3.159 Å / Redundancy: 2 % / Rmerge(I) obs: 0.7207 / Mean I/σ(I) obs: 0.96 / Num. unique obs: 1175 / CC1/2: 0.405 / % possible all: 94.26 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4R5Y Resolution: 3.05→62.54 Å / SU ML: 0.5714 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 33.7096
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 85.85 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 3.05→62.54 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION
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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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