+Open data
-Basic information
Entry | Database: PDB / ID: 6d5m | ||||||
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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 / 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 / oncogene-induced cell senescence / positive regulation of ruffle assembly / blood vessel morphogenesis / negative regulation of GTPase activity / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / positive regulation of epidermal growth factor receptor signaling pathway / T-helper 1 type immune response / epidermal growth factor receptor binding / Regulation of KIT signaling / positive regulation of wound healing / positive regulation of miRNA metabolic process / leukocyte migration / 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 / neurotrophin TRK receptor signaling pathway / GRB2:SOS provides linkage to MAPK signaling for Integrins / B cell homeostasis / RAS signaling downstream of NF1 loss-of-function variants / 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 / positive regulation of protein targeting to membrane / 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 / Estrogen-stimulated signaling through PRKCZ / adipose tissue development / Interleukin receptor SHC signaling / SHC-mediated cascade:FGFR3 / MET activates RAS signaling / : / Schwann cell development / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / 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 / 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 / FRS-mediated FGFR1 signaling / p38MAPK events / Tie2 Signaling / Signaling by FGFR2 in disease / RAC1 GTPase cycle / GRB2 events in EGFR signaling / EPHB-mediated forward signaling / SHC1 events in EGFR signaling / EGFR Transactivation by Gastrin / Signaling by FLT3 fusion proteins / FLT3 Signaling / myelination / Signaling by FGFR1 in disease / Ras activation upon Ca2+ influx through NMDA receptor / GRB2 events in ERBB2 signaling / NCAM signaling for neurite out-growth / CD209 (DC-SIGN) signaling / SHC1 events in ERBB2 signaling / Downstream signal transduction / FCERI mediated Ca+2 mobilization / Constitutive Signaling by Overexpressed ERBB2 / Insulin receptor signalling cascade / intrinsic apoptotic signaling pathway / GTPase activator activity / guanyl-nucleotide exchange factor activity / small monomeric GTPase / insulin-like growth factor receptor signaling pathway / G protein activity / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.081 Å | ||||||
Authors | Phan, J. / Hodges, T. / Fesik, S.W. | ||||||
Funding support | United States, 1items
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Citation | Journal: J. Med. Chem. / Year: 2018 Title: Discovery and Structure-Based Optimization of Benzimidazole-Derived Activators of SOS1-Mediated Nucleotide Exchange on RAS. Authors: Hodges, T.R. / Abbott, J.R. / Little, A.J. / Sarkar, D. / Salovich, J.M. / Howes, J.E. / Akan, D.T. / Sai, J. / Arnold, A.L. / Browning, C. / Burns, M.C. / Sobolik, T. / Sun, Q. / Beesetty, ...Authors: Hodges, T.R. / Abbott, J.R. / Little, A.J. / Sarkar, D. / Salovich, J.M. / Howes, J.E. / Akan, D.T. / Sai, J. / Arnold, A.L. / Browning, C. / Burns, M.C. / Sobolik, T. / Sun, Q. / Beesetty, Y. / Coker, J.A. / Scharn, D. / Stadtmueller, H. / Rossanese, O.W. / Phan, J. / Waterson, A.G. / McConnell, D.B. / 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 | 6d5m.cif.gz | 206.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6d5m.ent.gz | 156.6 KB | Display | PDB format |
PDBx/mmJSON format | 6d5m.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/d5/6d5m ftp://data.pdbj.org/pub/pdb/validation_reports/d5/6d5m | HTTPS FTP |
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-Related structure data
Related structure data | 6d55C 6d56C 6d59C 6d5eC 6d5gC 6d5hC 6d5jC 6d5lC 6d5vC 6d5wC 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 QRS
#1: Protein | Mass: 18840.146 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: 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 |
#3: 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 |
-Non-polymers , 4 types, 957 molecules
#4: Chemical | ChemComp-MG / |
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#5: Chemical | ChemComp-GNP / |
#6: Chemical | ChemComp-FW4 / |
#7: 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: 3.2 Å3/Da / Density % sol: 60 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / 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: Jul 19, 2014 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.98 Å / Relative weight: 1 |
Reflection | Resolution: 2.08→50 Å / Num. obs: 90229 / % possible obs: 100 % / Redundancy: 15 % / Rpim(I) all: 0.031 / Net I/σ(I): 25 |
Reflection shell | Resolution: 2.08→2.12 Å / Num. unique obs: 4458 / Rpim(I) all: 0.161 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4NYI Resolution: 2.081→35.008 Å / SU ML: 0.17 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 18.84
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.081→35.008 Å
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Refine LS restraints |
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LS refinement shell |
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