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Yorodumi- PDB-4nyi: Approach for Targeting Ras with Small Molecules that Activate SOS... -
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-Basic information
Entry | Database: PDB / ID: 4nyi | ||||||
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Title | Approach for Targeting Ras with Small Molecules that Activate SOS-Mediated Nucleotide Exchange | ||||||
Components |
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Keywords | SIGNALING PROTEIN / Ras SOS complex / signal transduction / Raf / PI3K / poly-petide / cytosol | ||||||
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: 2.9612 Å | ||||||
Authors | Burns, M.C. / Sun, Q. / Phan, J. / Fesik, S.W. | ||||||
Citation | Journal: Proc.Natl.Acad.Sci.USA / 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 | 4nyi.cif.gz | 182.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4nyi.ent.gz | 141.4 KB | Display | PDB format |
PDBx/mmJSON format | 4nyi.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ny/4nyi ftp://data.pdbj.org/pub/pdb/validation_reports/ny/4nyi | 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
-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: 56532.730 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, 147 molecules
#4: Chemical | ChemComp-MG / |
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#5: Chemical | ChemComp-GNP / |
#6: Chemical | ChemComp-2PX / |
#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: 3.96 Å3/Da / Density % sol: 68.94 % |
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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, VAPOR DIFFUSION, HANGING DROP, temperature 293K |
-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: Dec 5, 2012 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.98 Å / Relative weight: 1 |
Reflection | Resolution: 2.961→35.945 Å / Num. all: 31718 / Num. obs: 31718 / % possible obs: 100 % |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.9612→35.945 Å / SU ML: 0.31 / σ(F): 0 / Phase error: 20.73 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.9612→35.945 Å
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Refine LS restraints |
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LS refinement shell |
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