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- PDB-5ovh: Ras guanine nucleotide exchange factor SOS1 (Rem-cdc25) in comple... -
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Open data
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Basic information
Entry | Database: PDB / ID: 5ovh | ||||||
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Title | Ras guanine nucleotide exchange factor SOS1 (Rem-cdc25) in complex with small molecule inhibitor compound 21 | ||||||
![]() | Son of sevenless homolog 1 | ||||||
![]() | SIGNALING PROTEIN / Guanine exchange factor / GEF / inhibitor / SOS1 | ||||||
Function / homology | ![]() 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 / Signaling by LTK / positive regulation of epidermal growth factor receptor signaling pathway / Regulation of KIT signaling / epidermal growth factor receptor binding / leukocyte migration / regulation of T cell proliferation / NRAGE signals death through JNK / roof of mouth development / eyelid development in camera-type eye / Fc-epsilon receptor signaling pathway / GRB2:SOS provides linkage to MAPK signaling for Integrins / B cell homeostasis / neurotrophin TRK receptor signaling pathway / 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 / Interleukin receptor SHC signaling / Signal attenuation / SHC-mediated cascade:FGFR3 / MET activates RAS signaling / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / Schwann cell development / SHC-mediated cascade:FGFR2 / SHC-mediated cascade:FGFR4 / Signaling by FGFR4 in disease / Erythropoietin activates RAS / SHC-mediated cascade:FGFR1 / FRS-mediated FGFR3 signaling / Signaling by FLT3 ITD and TKD mutants / FRS-mediated FGFR2 signaling / Signaling by FGFR3 in disease / FRS-mediated FGFR4 signaling / Tie2 Signaling / FRS-mediated FGFR1 signaling / Signaling by FGFR2 in disease / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / EGFR Transactivation by Gastrin / Signaling by FLT3 fusion proteins / RAC1 GTPase cycle / 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 / Constitutive Signaling by Overexpressed ERBB2 / FCERI mediated Ca+2 mobilization / Insulin receptor signalling cascade / GTPase activator activity / insulin-like growth factor receptor signaling pathway / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / molecular condensate scaffold activity / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / guanyl-nucleotide exchange factor activity / axon guidance / response to ischemia / FCERI mediated MAPK activation / Signaling by ERBB2 TMD/JMD mutants / B cell receptor signaling pathway / 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 / insulin receptor signaling pathway / DAP12 signaling / Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants / regulation of cell population proliferation / RAF/MAP kinase cascade / Ras protein signal transduction / Potential therapeutics for SARS / protein heterodimerization activity Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | 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. | ||||||
![]() | ![]() 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: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 118.4 KB | Display | ![]() |
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PDB format | ![]() | 88.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 5ovdC ![]() 5oveC ![]() 5ovfC ![]() 5ovgC ![]() 5oviC ![]() 6eieC ![]() 6eplC ![]() 6epmC ![]() 6epnC ![]() 6epoC ![]() 6eppC ![]() 2ii0S S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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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.) ![]() ![]() ![]() | ||
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#2: Chemical | ChemComp-AWW / [ | ||
#3: Chemical | #4: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.71 Å3/Da / Density % sol: 54.69 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: Protein concentration 30.7 mg/ml. Protein buffer 25 Millimolar TRIS-HCL PH 7.5, 50 millimolar NaCl, 1 millimolar DTT. Reservoir 23% (v/v) ethylenglycol. Protein incubated with 5 MILLIMOLAR ...Details: Protein concentration 30.7 mg/ml. Protein buffer 25 Millimolar TRIS-HCL PH 7.5, 50 millimolar NaCl, 1 millimolar DTT. Reservoir 23% (v/v) ethylenglycol. Protein incubated with 5 MILLIMOLAR LIGAND overnight at 277K prior to crystallization. |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Aug 20, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.91841 Å / Relative weight: 1 |
Reflection | Resolution: 2.3→48.4 Å / Num. obs: 28560 / % possible obs: 99.5 % / Redundancy: 5.3 % / Biso Wilson estimate: 45.4 Å2 / CC1/2: 0.999 / Rsym value: 0.051 / Net I/σ(I): 22.13 |
Reflection shell | Resolution: 2.3→2.44 Å / Redundancy: 5.33 % / Mean I/σ(I) obs: 4.86 / Num. unique obs: 4505 / CC1/2: 0.94 / Rsym value: 0.328 / % possible all: 98.8 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 2ii0 Resolution: 2.3→44.06 Å / Cor.coef. Fo:Fc: 0.894 / Cor.coef. Fo:Fc free: 0.813 / SU B: 10.081 / SU ML: 0.246 / Cross valid method: THROUGHOUT / ESU R: 0.38 / ESU R Free: 0.302 / Stereochemistry target values: MAXIMUM LIKELIHOOD / 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 / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 49.569 Å2
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Refinement step | Cycle: 1 / Resolution: 2.3→44.06 Å
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Refine LS restraints |
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