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Yorodumi- PDB-5ovi: Ras guanine nucleotide exchange factor SOS1 (Rem-cdc25) in comple... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5ovi | ||||||
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Title | Ras guanine nucleotide exchange factor SOS1 (Rem-cdc25) in complex with small molecule inhibitor BAY-293 (compound 23) | ||||||
Components | Son of sevenless homolog 1 | ||||||
Keywords | SIGNALING PROTEIN / Guanine exchange factor / GEF / inhibitor / SOS1 | ||||||
Function / homology | Function and homology information midbrain morphogenesis / regulation of pro-B cell differentiation / vitellogenesis / pericardium morphogenesis / cardiac atrium morphogenesis / heart trabecula morphogenesis / regulation of T cell differentiation in thymus / GTPase complex / positive regulation of small GTPase mediated signal transduction / Interleukin-15 signaling ...midbrain morphogenesis / regulation of pro-B cell differentiation / vitellogenesis / pericardium morphogenesis / cardiac atrium morphogenesis / heart trabecula morphogenesis / regulation of T cell differentiation in thymus / GTPase complex / positive regulation of small GTPase mediated signal transduction / Interleukin-15 signaling / Activation of RAC1 / blood vessel morphogenesis / positive regulation of epidermal growth factor receptor signaling pathway / epidermal growth factor receptor binding / Regulation of KIT signaling / leukocyte migration / NRAGE signals death through JNK / regulation of T cell proliferation / roof of mouth development / eyelid development in camera-type eye / Fc-epsilon receptor signaling pathway / neurotrophin TRK receptor signaling pathway / GRB2:SOS provides linkage to MAPK signaling for Integrins / B cell homeostasis / SOS-mediated signalling / RET signaling / Activated NTRK3 signals through RAS / Activated NTRK2 signals through RAS / hair follicle development / SHC1 events in ERBB4 signaling / Signalling to RAS / fibroblast growth factor receptor signaling pathway / SHC-related events triggered by IGF1R / Activated NTRK2 signals through FRS2 and FRS3 / Role of LAT2/NTAL/LAB on calcium mobilization / Signal attenuation / Interleukin receptor SHC signaling / SHC-mediated cascade:FGFR3 / MET activates RAS signaling / Schwann cell development / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / SHC-mediated cascade:FGFR2 / SHC-mediated cascade:FGFR4 / Signaling by FGFR4 in disease / SHC-mediated cascade:FGFR1 / Erythropoietin activates RAS / FRS-mediated FGFR3 signaling / Signaling by FLT3 ITD and TKD mutants / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / Signaling by FGFR3 in disease / FRS-mediated FGFR1 signaling / Tie2 Signaling / Signaling by FGFR2 in disease / RAC1 GTPase cycle / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / EGFR Transactivation by Gastrin / Signaling by FLT3 fusion proteins / FLT3 Signaling / myelination / Signaling by FGFR1 in disease / GRB2 events in ERBB2 signaling / NCAM signaling for neurite out-growth / SHC1 events in ERBB2 signaling / Downstream signal transduction / FCERI mediated Ca+2 mobilization / Constitutive Signaling by Overexpressed ERBB2 / Insulin receptor signalling cascade / GTPase activator activity / guanyl-nucleotide exchange factor activity / insulin-like growth factor receptor signaling pathway / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / molecular condensate scaffold activity / response to ischemia / FCERI mediated MAPK activation / axon guidance / B cell receptor signaling pathway / Signaling by ERBB2 TMD/JMD mutants / Constitutive Signaling by EGFRvIII / Signaling by ERBB2 ECD mutants / epidermal growth factor receptor signaling pathway / Signaling by ERBB2 KD Mutants / Signaling by SCF-KIT / multicellular organism growth / cytokine-mediated signaling pathway / SH3 domain binding / Signaling by CSF1 (M-CSF) in myeloid cells / G alpha (12/13) signalling events / DAP12 signaling / Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants / insulin receptor signaling pathway / regulation of cell population proliferation / RAF/MAP kinase cascade / Ras protein signal transduction / Potential therapeutics for SARS / protein heterodimerization activity / neuronal cell body Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.2 Å | ||||||
Authors | Hillig, R.C. / Sautier, B. / Schroeder, J. / Moosmayer, D. / Hilpmann, A. / Stegmann, C.M. / Briem, H. / Boemer, U. / Weiske, J. / Badock, V. ...Hillig, R.C. / Sautier, B. / Schroeder, J. / Moosmayer, D. / Hilpmann, A. / Stegmann, C.M. / Briem, H. / Boemer, U. / Weiske, J. / Badock, V. / Petersen, K. / Kahmann, J. / Wegener, D. / Bohnke, N. / Eis, K. / Graham, K. / Wortmann, L. / von Nussbaum, F. / Bader, B. | ||||||
Citation | Journal: Proc. Natl. Acad. Sci. U.S.A. / Year: 2019 Title: Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS-SOS1 interaction. Authors: Hillig, R.C. / Sautier, B. / Schroeder, J. / Moosmayer, D. / Hilpmann, A. / Stegmann, C.M. / Werbeck, N.D. / Briem, H. / Boemer, U. / Weiske, J. / Badock, V. / Mastouri, J. / Petersen, K. / ...Authors: Hillig, R.C. / Sautier, B. / Schroeder, J. / Moosmayer, D. / Hilpmann, A. / Stegmann, C.M. / Werbeck, N.D. / Briem, H. / Boemer, U. / Weiske, J. / Badock, V. / Mastouri, J. / Petersen, K. / Siemeister, G. / Kahmann, J.D. / Wegener, D. / Bohnke, N. / Eis, K. / Graham, K. / Wortmann, L. / von Nussbaum, F. / Bader, B. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5ovi.cif.gz | 217.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5ovi.ent.gz | 171.7 KB | Display | PDB format |
PDBx/mmJSON format | 5ovi.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ov/5ovi ftp://data.pdbj.org/pub/pdb/validation_reports/ov/5ovi | HTTPS FTP |
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-Related structure data
Related structure data | 5ovdC 5oveC 5ovfC 5ovgC 5ovhC 6eieC 6eplC 6epmC 6epnC 6epoC 6eppC 2ii0S 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: 57376.637 Da / Num. of mol.: 1 / Mutation: Q560G, E561A, E562M, K563A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SOS1 / Production host: Escherichia coli (E. coli) / References: UniProt: Q07889 | ||
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#2: Chemical | ChemComp-AXH / | ||
#3: Chemical | #4: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.54 Å3/Da / Density % sol: 51.59 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8.5 Details: Protein concentration 30.7 mg/ml. Protein buffer 25 Millimolar TRIS-HCL PH 7.5, 50 millimolar NaCl, 1 millimolar DTT. Reservoir 0.1 M TRIS pH 8.5, 25 % (w/v) PEG 3350. CRYO BUFFER WAS ...Details: Protein concentration 30.7 mg/ml. Protein buffer 25 Millimolar TRIS-HCL PH 7.5, 50 millimolar NaCl, 1 millimolar DTT. Reservoir 0.1 M TRIS pH 8.5, 25 % (w/v) PEG 3350. CRYO BUFFER WAS RESERVOIR SUPPLEMENTED WITH 2 MILLIMOLAR INHIBITOR (FROM 100 MILLIMOLAR DMSO STOCK) AND 15 % (v/v) ETHYLENE GLYCOL |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: BESSY / Beamline: 14.1 / Wavelength: 0.91841 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Mar 2, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.91841 Å / Relative weight: 1 |
Reflection | Resolution: 2.2→48.02 Å / Num. all: 112189 / Num. obs: 30220 / % possible obs: 98.5 % / Redundancy: 3.71 % / Biso Wilson estimate: 41.9 Å2 / CC1/2: 0.984 / Rsym value: 0.14 / Net I/σ(I): 5.75 |
Reflection shell | Resolution: 2.2→2.33 Å / Redundancy: 3.79 % / Mean I/σ(I) obs: 1.54 / Num. unique obs: 4836 / CC1/2: 0.674 / Rsym value: 0.644 / % possible all: 99.5 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2ii0 Resolution: 2.2→48.02 Å / Cor.coef. Fo:Fc: 0.943 / Cor.coef. Fo:Fc free: 0.918 / SU B: 13.937 / SU ML: 0.181 / Cross valid method: THROUGHOUT / ESU R: 0.286 / ESU R Free: 0.216 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 42.192 Å2
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Refinement step | Cycle: 1 / Resolution: 2.2→48.02 Å
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Refine LS restraints |
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