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Yorodumi- PDB-7juy: Crystal Structure of KSR1:MEK1 in complex with AMP-PNP, and allos... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7juy | |||||||||
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Title | Crystal Structure of KSR1:MEK1 in complex with AMP-PNP, and allosteric MEK inhibitor Cobimetinib | |||||||||
Components |
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Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / Kinase / Pseudokinase / drug target / cell signaling and cancer / TRANSFERASE / TRANSFERASE-TRANSFERASE INHIBITOR complex | |||||||||
Function / homology | Function and homology information regulation of MAP kinase activity / mitogen-activated protein kinase kinase / MAP-kinase scaffold activity / spindle pole body / regulation of Golgi inheritance / regulation of early endosome to late endosome transport / regulation of stress-activated MAPK cascade / MAP kinase kinase activity / 14-3-3 protein binding / cAMP-mediated signaling ...regulation of MAP kinase activity / mitogen-activated protein kinase kinase / MAP-kinase scaffold activity / spindle pole body / regulation of Golgi inheritance / regulation of early endosome to late endosome transport / regulation of stress-activated MAPK cascade / MAP kinase kinase activity / 14-3-3 protein binding / cAMP-mediated signaling / RAF activation / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / ruffle membrane / 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 / Signaling by BRAF and RAF1 fusions / late endosome / regulation of cell population proliferation / protein tyrosine kinase activity / Ras protein signal transduction / positive regulation of MAPK cascade / phosphorylation / early endosome / non-specific serine/threonine protein kinase / protein kinase activity / intracellular membrane-bounded organelle / protein serine kinase activity / focal adhesion / protein serine/threonine kinase activity / centrosome / endoplasmic reticulum membrane / endoplasmic reticulum / protein-containing complex / mitochondrion / ATP binding / membrane / nucleus / metal ion binding / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) Oryctolagus cuniculus (rabbit) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.096 Å | |||||||||
Authors | Khan, Z.M. / Dar, A.C. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Nature / Year: 2020 Title: Structural basis for the action of the drug trametinib at KSR-bound MEK. Authors: Khan, Z.M. / Real, A.M. / Marsiglia, W.M. / Chow, A. / Duffy, M.E. / Yerabolu, J.R. / Scopton, A.P. / Dar, A.C. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7juy.cif.gz | 140.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7juy.ent.gz | 104.2 KB | Display | PDB format |
PDBx/mmJSON format | 7juy.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7juy_validation.pdf.gz | 2 MB | Display | wwPDB validaton report |
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Full document | 7juy_full_validation.pdf.gz | 2 MB | Display | |
Data in XML | 7juy_validation.xml.gz | 24.7 KB | Display | |
Data in CIF | 7juy_validation.cif.gz | 32.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ju/7juy ftp://data.pdbj.org/pub/pdb/validation_reports/ju/7juy | HTTPS FTP |
-Related structure data
Related structure data | 7juqC 7jurC 7jusC 7jutC 7juuC 7juvC 7juwC 7juxC 7juzC 7jv0C 7jv1C 2y4iS 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
-Protein , 2 types, 2 molecules BC
#1: Protein | Mass: 38597.137 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KSR1, KSR / Plasmid: pFastBac Dual / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: Q8IVT5, non-specific serine/threonine protein kinase |
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#2: Protein | Mass: 43119.371 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Oryctolagus cuniculus (rabbit) / Gene: MAP2K1, MEK1, PRKMK1 / Plasmid: pFastBac Dual / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P29678, mitogen-activated protein kinase kinase |
-Non-polymers , 4 types, 6 molecules
#3: Chemical | #4: Chemical | #5: Chemical | ChemComp-EUI / [ | #6: Water | ChemComp-HOH / | |
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-Details
Compound details | The author states that kinase suppressor of Ras 1 chain B is proteolytically cleaved between Trp632 ...The author states that kinase suppressor of Ras 1 chain B is proteolytically cleaved between Trp632 and His633. |
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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: 3.58 Å3/Da / Density % sol: 65.62 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / Details: PEG 2000, MES, pH 6.5, Magnesium acetate |
-Data collection
Diffraction | Mean temperature: 80 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 21-ID-F / Wavelength: 1 Å |
Detector | Type: RAYONIX MX-300 / Detector: CCD / Date: Aug 19, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 3.096→49.648 Å / Num. obs: 22409 / % possible obs: 99.9 % / Redundancy: 11.95 % / CC1/2: 1 / Net I/σ(I): 20.04 |
Reflection shell | Resolution: 3.1→3.18 Å / Num. unique obs: 1608 / CC1/2: 0.519 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2Y4I Resolution: 3.096→49.648 Å / SU ML: 0.46 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 30.17 / 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: 3.096→49.648 Å
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Refine LS restraints |
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LS refinement shell |
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