+Open data
-Basic information
Entry | Database: PDB / ID: 6scm | ||||||
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Title | SOS1 in Complex with Inhibitor BI-3406 | ||||||
Components | Son of sevenless homolog 1 | ||||||
Keywords | ONCOPROTEIN / Oncology / exchange factor / protein-ligand complex | ||||||
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 / Regulation of KIT signaling / epidermal growth factor receptor binding / 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 / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / RAC1 GTPase cycle / EGFR Transactivation by Gastrin / myelination / Signaling by FLT3 fusion proteins / FLT3 Signaling / GRB2 events in ERBB2 signaling / Signaling by FGFR1 in disease / NCAM signaling for neurite out-growth / GTPase activator activity / SHC1 events in ERBB2 signaling / Downstream signal transduction / Constitutive Signaling by Overexpressed ERBB2 / FCERI mediated Ca+2 mobilization / molecular condensate scaffold activity / Insulin receptor signalling cascade / 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 / response to ischemia / axon guidance / FCERI mediated MAPK activation / Signaling by ERBB2 TMD/JMD mutants / B cell receptor signaling pathway / multicellular organism growth / Constitutive Signaling by EGFRvIII / Signaling by ERBB2 ECD mutants / epidermal growth factor receptor signaling pathway / Signaling by ERBB2 KD Mutants / Signaling by SCF-KIT / SH3 domain binding / cytokine-mediated signaling pathway / Signaling by CSF1 (M-CSF) in myeloid cells / G alpha (12/13) signalling events / Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants / DAP12 signaling / 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: 1.866 Å | ||||||
Authors | Kessler, D. / Fischer, G. / Ramharter, J. | ||||||
Citation | Journal: Cancer Discov / Year: 2021 Title: BI-3406, a Potent and Selective SOS1-KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition. Authors: Hofmann, M.H. / Gmachl, M. / Ramharter, J. / Savarese, F. / Gerlach, D. / Marszalek, J.R. / Sanderson, M.P. / Kessler, D. / Trapani, F. / Arnhof, H. / Rumpel, K. / Botesteanu, D.A. / ...Authors: Hofmann, M.H. / Gmachl, M. / Ramharter, J. / Savarese, F. / Gerlach, D. / Marszalek, J.R. / Sanderson, M.P. / Kessler, D. / Trapani, F. / Arnhof, H. / Rumpel, K. / Botesteanu, D.A. / Ettmayer, P. / Gerstberger, T. / Kofink, C. / Wunberg, T. / Zoephel, A. / Fu, S.C. / Teh, J.L. / Bottcher, J. / Pototschnig, N. / Schachinger, F. / Schipany, K. / Lieb, S. / Vellano, C.P. / O'Connell, J.C. / Mendes, R.L. / Moll, J. / Petronczki, M. / Heffernan, T.P. / Pearson, M. / McConnell, D.B. / Kraut, N. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6scm.cif.gz | 308.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6scm.ent.gz | 241.7 KB | Display | PDB format |
PDBx/mmJSON format | 6scm.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/sc/6scm ftp://data.pdbj.org/pub/pdb/validation_reports/sc/6scm | HTTPS FTP |
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-Related 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: 57103.285 Da / Num. of mol.: 1 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 | #3: Chemical | ChemComp-EDO / #4: Chemical | ChemComp-L7H / ~{ | #5: Water | ChemComp-HOH / | 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: 2.21 Å3/Da / Density % sol: 44.43 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 8 / Details: 13% PEG8000, 0.1M Imidazole pH=8.0 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å |
Detector | Type: DECTRIS EIGER X 4M / Detector: PIXEL / Date: Aug 8, 2016 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.866→84.462 Å / Num. obs: 34879 / % possible obs: 80.6 % / Redundancy: 9.6 % / CC1/2: 0.998 / Rmerge(I) obs: 0.132 / Rpim(I) all: 0.044 / Net I/σ(I): 12 |
Reflection shell | Resolution: 1.866→1.981 Å / Num. unique obs: 1744 / CC1/2: 0.342 / Rpim(I) all: 0.694 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.866→84.46 Å / Cor.coef. Fo:Fc: 0.941 / Cor.coef. Fo:Fc free: 0.928 / SU R Cruickshank DPI: 0.65 / Cross valid method: THROUGHOUT / SU R Blow DPI: 0.217 / SU Rfree Blow DPI: 0.16 / SU Rfree Cruickshank DPI: 0.156
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Displacement parameters | Biso mean: 32.1 Å2
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Refine analyze | Luzzati coordinate error obs: 0.27 Å | ||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.866→84.46 Å
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LS refinement shell | Resolution: 1.84→1.94 Å
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Refinement TLS params. | Origin x: 8.7326 Å / Origin y: -15.3206 Å / Origin z: -22.1583 Å
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Refinement TLS group | Selection details: { A|* } |