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Yorodumi- PDB-7m0v: Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7m0v | ||||||||||||
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Title | Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and Cobimetinib | ||||||||||||
Components |
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Keywords | TRANSFERASE / BRAF / MEK1 | ||||||||||||
Function / homology | Function and homology information epithelial cell proliferation involved in lung morphogenesis / positive regulation of endodermal cell differentiation / CD4-positive, alpha-beta T cell differentiation / placenta blood vessel development / regulation of axon regeneration / mitogen-activated protein kinase kinase / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative regulation of synaptic vesicle exocytosis / labyrinthine layer development / MAP-kinase scaffold activity ...epithelial cell proliferation involved in lung morphogenesis / positive regulation of endodermal cell differentiation / CD4-positive, alpha-beta T cell differentiation / placenta blood vessel development / regulation of axon regeneration / mitogen-activated protein kinase kinase / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative regulation of synaptic vesicle exocytosis / labyrinthine layer development / MAP-kinase scaffold activity / type B pancreatic cell proliferation / Signalling to p38 via RIT and RIN / cerebellar cortex formation / 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 / Signaling by MAP2K mutants / negative regulation of fibroblast migration / positive regulation of D-glucose transmembrane transport / establishment of protein localization to membrane / regulation of Golgi inheritance / spindle pole body / mitogen-activated protein kinase kinase binding / regulation of T cell differentiation / trachea formation / Negative feedback regulation of MAPK pathway / regulation of early endosome to late endosome transport / positive regulation of axonogenesis / regulation of stress-activated MAPK cascade / Frs2-mediated activation / stress fiber assembly / ERBB2-ERBB3 signaling pathway / protein kinase activator activity / positive regulation of axon regeneration / MAPK3 (ERK1) activation / endodermal cell differentiation / face development / MAP kinase kinase activity / synaptic vesicle exocytosis / Bergmann glial cell differentiation / somatic stem cell population maintenance / thyroid gland development / Uptake and function of anthrax toxins / MAP kinase kinase kinase activity / negative regulation of endothelial cell apoptotic process / Schwann cell development / positive regulation of substrate adhesion-dependent cell spreading / keratinocyte differentiation / positive regulation of stress fiber assembly / response to cAMP / protein serine/threonine/tyrosine kinase activity / myelination / ERK1 and ERK2 cascade / cellular response to calcium ion / substrate adhesion-dependent cell spreading / protein serine/threonine kinase activator activity / insulin-like growth factor receptor signaling pathway / MAP3K8 (TPL2)-dependent MAPK1/3 activation / cellular response to nerve growth factor stimulus / thymus development / Signal transduction by L1 / cell motility / animal organ morphogenesis / long-term synaptic potentiation / RAF activation / Spry regulation of FGF signaling / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / epidermal growth factor receptor signaling pathway / visual learning / positive regulation of protein serine/threonine kinase activity / neuron differentiation / 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 / chemotaxis / cellular senescence / MAPK cascade / Signaling by BRAF and RAF1 fusions / cellular response to xenobiotic stimulus / late endosome / positive regulation of peptidyl-serine phosphorylation / presynapse / heart development / T cell receptor signaling pathway / regulation of cell population proliferation / T cell differentiation in thymus / cell body / scaffold protein binding / protein tyrosine kinase activity / negative regulation of neuron apoptotic process / positive regulation of ERK1 and ERK2 cascade / early endosome / non-specific serine/threonine protein kinase Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.16 Å | ||||||||||||
Authors | Li, K. / Gonzalez Del-Pino, G. / Ha, B.H. / Park, E. / Eck, M.J. | ||||||||||||
Funding support | United States, 3items
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Citation | Journal: Proc.Natl.Acad.Sci.USA / Year: 2021 Title: Allosteric MEK inhibitors act on BRAF/MEK complexes to block MEK activation. Authors: Gonzalez-Del Pino, G.L. / Li, K. / Park, E. / Schmoker, A.M. / Ha, B.H. / Eck, M.J. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7m0v.cif.gz | 255.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7m0v.ent.gz | 204.9 KB | Display | PDB format |
PDBx/mmJSON format | 7m0v.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7m0v_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 7m0v_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 7m0v_validation.xml.gz | 24.2 KB | Display | |
Data in CIF | 7m0v_validation.cif.gz | 32.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/m0/7m0v ftp://data.pdbj.org/pub/pdb/validation_reports/m0/7m0v | HTTPS FTP |
-Related structure data
Related structure data | 6v2wC 7m0tC 7m0uC 7m0wC 7m0xC 7m0yC 7m0zC 6pp9S 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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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 32098.104 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BRAF, BRAF1, RAFB1 / Plasmid: PFASTBAC DUAL / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P15056, non-specific serine/threonine protein kinase | ||||||
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#2: Protein | Mass: 43790.281 Da / Num. of mol.: 1 / Mutation: S218A, S222A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MAP2K1, MEK1, PRKMK1 / Plasmid: pAC8 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: Q02750, mitogen-activated protein kinase kinase | ||||||
#3: Chemical | #4: Chemical | #5: Chemical | ChemComp-EUI / [ | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.33 Å3/Da / Density % sol: 63.09 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8.5 Details: 100 mM Tris 8.5, 200 mM Lithium Sulfate and 22% PEG 3,350 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 24-ID-C / Wavelength: 0.979 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Nov 13, 2019 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.979 Å / Relative weight: 1 |
Reflection | Resolution: 3.16→43.3 Å / Num. obs: 17794 / % possible obs: 99.88 % / Redundancy: 19.6 % / Biso Wilson estimate: 111.13 Å2 / CC1/2: 1 / Rmerge(I) obs: 0.1543 / Rpim(I) all: 0.03577 / Rrim(I) all: 0.1543 / Net I/σ(I): 18.76 |
Reflection shell | Resolution: 3.16→3.273 Å / Mean I/σ(I) obs: 1.63 / Num. unique obs: 1747 / CC1/2: 0.745 / Rpim(I) all: 0.472 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6PP9 Resolution: 3.16→43.3 Å / SU ML: 0.4 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 25.72 / 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 208.16 Å2 / Biso mean: 107.1681 Å2 / Biso min: 66.65 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 3.16→43.3 Å
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 6 / % reflection obs: 100 %
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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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