+Open data
-Basic information
Entry | Database: PDB / ID: 6cur | ||||||
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Title | Ras:SOS:Ras in complex with a small molecule activator | ||||||
Components |
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Keywords | SIGNALING PROTEIN / Ras / SOS / inhibitor / ONCOPROTEIN / Protein-protein complex / MAPK | ||||||
Function / homology | Function and homology information midbrain morphogenesis / regulation of pro-B cell differentiation / vitellogenesis / pericardium morphogenesis / cardiac atrium morphogenesis / heart trabecula morphogenesis / phospholipase C activator activity / regulation of T cell differentiation in thymus / GTPase complex / Interleukin-15 signaling ...midbrain morphogenesis / regulation of pro-B cell differentiation / vitellogenesis / pericardium morphogenesis / cardiac atrium morphogenesis / heart trabecula morphogenesis / phospholipase C activator activity / regulation of T cell differentiation in thymus / GTPase complex / Interleukin-15 signaling / positive regulation of small GTPase mediated signal transduction / Activation of RAC1 / oncogene-induced cell senescence / positive regulation of ruffle assembly / blood vessel morphogenesis / Signaling by LTK / negative regulation of GTPase activity / positive regulation of miRNA metabolic process / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / positive regulation of epidermal growth factor receptor signaling pathway / Regulation of KIT signaling / epidermal growth factor receptor binding / T-helper 1 type immune response / leukocyte migration / positive regulation of wound healing / NRAGE signals death through JNK / regulation of T cell proliferation / roof of mouth development / eyelid development in camera-type eye / defense response to protozoan / Fc-epsilon receptor signaling pathway / Signaling by RAS GAP mutants / Signaling by RAS GTPase mutants / Activation of RAS in B cells / GRB2:SOS provides linkage to MAPK signaling for Integrins / B cell homeostasis / neurotrophin TRK receptor signaling pathway / RAS signaling downstream of NF1 loss-of-function variants / RET signaling / SOS-mediated signalling / Activated NTRK3 signals through RAS / Activated NTRK2 signals through RAS / hair follicle development / SHC1 events in ERBB4 signaling / positive regulation of protein targeting to membrane / Signalling to RAS / fibroblast growth factor receptor signaling pathway / Role of LAT2/NTAL/LAB on calcium mobilization / SHC-related events triggered by IGF1R / Activated NTRK2 signals through FRS2 and FRS3 / Interleukin receptor SHC signaling / adipose tissue development / Signal attenuation / Estrogen-stimulated signaling through PRKCZ / SHC-mediated cascade:FGFR3 / MET activates RAS signaling / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / SHC-mediated cascade:FGFR2 / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / Schwann cell development / SHC-mediated cascade:FGFR4 / Signaling by FGFR4 in disease / Erythropoietin activates RAS / SHC-mediated cascade:FGFR1 / protein-membrane adaptor activity / FRS-mediated FGFR3 signaling / Signaling by FLT3 ITD and TKD mutants / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / Signaling by FGFR3 in disease / p38MAPK events / Tie2 Signaling / FRS-mediated FGFR1 signaling / Signaling by FGFR2 in disease / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / EPHB-mediated forward signaling / EGFR Transactivation by Gastrin / Signaling by FLT3 fusion proteins / RAC1 GTPase cycle / FLT3 Signaling / Signaling by FGFR1 in disease / myelination / GRB2 events in ERBB2 signaling / CD209 (DC-SIGN) signaling / Ras activation upon Ca2+ influx through NMDA receptor / NCAM signaling for neurite out-growth / SHC1 events in ERBB2 signaling / Downstream signal transduction / intrinsic apoptotic signaling pathway / Constitutive Signaling by Overexpressed ERBB2 / Insulin receptor signalling cascade / FCERI mediated Ca+2 mobilization / GTPase activator activity / insulin-like growth factor receptor signaling pathway / positive regulation of GTPase activity / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / T cell activation / positive regulation of epithelial cell proliferation Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.73 Å | ||||||
Authors | Phan, J. / Abbott, J. / Fesik, S.W. | ||||||
Funding support | United States, 1items
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Citation | Journal: ACS Med Chem Lett / Year: 2018 Title: Discovery of Quinazolines That Activate SOS1-Mediated Nucleotide Exchange on RAS. Authors: Abbott, J.R. / Patel, P.A. / Howes, J.E. / Akan, D.T. / Kennedy, J.P. / Burns, M.C. / Browning, C.F. / Sun, Q. / Rossanese, O.W. / Phan, J. / Waterson, A.G. / Fesik, S.W. #1: Journal: Proc. Natl. Acad. Sci. U.S.A. / Year: 2014 Title: Approach for targeting Ras with small molecules that activate SOS-mediated nucleotide exchange. Authors: Burns, M.C. / Sun, Q. / Daniels, R.N. / Camper, D. / Kennedy, J.P. / Phan, J. / Olejniczak, E.T. / Lee, T. / Waterson, A.G. / Rossanese, O.W. / Fesik, S.W. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6cur.cif.gz | 380.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6cur.ent.gz | 303.2 KB | Display | PDB format |
PDBx/mmJSON format | 6cur.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6cur_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 6cur_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 6cur_validation.xml.gz | 44.5 KB | Display | |
Data in CIF | 6cur_validation.cif.gz | 69.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cu/6cur ftp://data.pdbj.org/pub/pdb/validation_reports/cu/6cur | HTTPS FTP |
-Related structure data
Related structure data | 6cuoC 6cupC 4nyiS 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 on special symmetry positions |
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-Components
-Protein , 3 types, 3 molecules ABC
#1: Protein | Mass: 18856.146 Da / Num. of mol.: 1 / Mutation: Y64A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HRAS, HRAS1 / Production host: Escherichia coli (E. coli) / References: UniProt: P01112 |
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#2: Protein | Mass: 56589.781 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 |
#3: Protein | Mass: 18932.242 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HRAS, HRAS1 / Production host: Escherichia coli (E. coli) / References: UniProt: P01112 |
-Non-polymers , 7 types, 1265 molecules
#4: Chemical | ChemComp-GNP / | ||||||
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#5: Chemical | ChemComp-MG / | ||||||
#6: Chemical | ChemComp-FFY / | ||||||
#7: Chemical | ChemComp-FMT / #8: Chemical | #9: Chemical | ChemComp-NA / | #10: Water | ChemComp-HOH / | |
-Details
Has protein modification | Y |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 4 Å3/Da / Density % sol: 69 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 4 / Details: 0.1 M sodium acetate, 2.0 M sodium formate, pH 4.0 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 21-ID-F / Wavelength: 0.98 Å |
Detector | Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Jan 31, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.98 Å / Relative weight: 1 |
Reflection | Resolution: 1.73→50 Å / Num. obs: 158342 / % possible obs: 100 % / Redundancy: 11.4 % / Rpim(I) all: 0.029 / Net I/σ(I): 22.11 |
Reflection shell | Resolution: 1.73→1.76 Å / Rpim(I) all: 0.316 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4NYI Resolution: 1.73→35.166 Å / SU ML: 0.17 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 17.25
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.73→35.166 Å
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Refine LS restraints |
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LS refinement shell |
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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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