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Yorodumi- PDB-6wm1: Crystal structure of the Grb2 SH2 domain in complex with a tripep... -
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-Basic information
Entry | Database: PDB / ID: 6wm1 | |||||||||||||||
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Title | Crystal structure of the Grb2 SH2 domain in complex with a tripeptide: Ac-pY-Ac6c-N-phenylpropyl | |||||||||||||||
Components |
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Keywords | PEPTIDE BINDING PROTEIN / Grb2 SH2 Ligand preorganization | |||||||||||||||
Function / homology | Function and homology information guanyl-nucleotide exchange factor adaptor activity / Grb2-EGFR complex / branching involved in labyrinthine layer morphogenesis / STAT5 Activation / COP9 signalosome / neurotrophin TRKA receptor binding / Activated NTRK2 signals through PI3K / vesicle membrane / MET receptor recycling / transmembrane receptor protein tyrosine kinase adaptor activity ...guanyl-nucleotide exchange factor adaptor activity / Grb2-EGFR complex / branching involved in labyrinthine layer morphogenesis / STAT5 Activation / COP9 signalosome / neurotrophin TRKA receptor binding / Activated NTRK2 signals through PI3K / vesicle membrane / MET receptor recycling / transmembrane receptor protein tyrosine kinase adaptor activity / Signaling by cytosolic FGFR1 fusion mutants / Interleukin-15 signaling / MET activates PTPN11 / MET activates RAP1 and RAC1 / CD28 dependent Vav1 pathway / Costimulation by the CD28 family / MET activates PI3K/AKT signaling / Signal regulatory protein family interactions / epidermal growth factor receptor binding / Regulation of KIT signaling / positive regulation of actin filament polymerization / PI-3K cascade:FGFR3 / STAT5 activation downstream of FLT3 ITD mutants / PI-3K cascade:FGFR2 / PI-3K cascade:FGFR4 / PI-3K cascade:FGFR1 / endodermal cell differentiation / regulation of MAPK cascade / GRB2:SOS provides linkage to MAPK signaling for Integrins / RHOU GTPase cycle / PI3K events in ERBB2 signaling / SOS-mediated signalling / RET signaling / Activated NTRK3 signals through RAS / Activated NTRK2 signals through RAS / insulin receptor substrate binding / Interleukin-3, Interleukin-5 and GM-CSF signaling / PI3K Cascade / SHC1 events in ERBB4 signaling / RHO GTPases Activate WASPs and WAVEs / Signalling to RAS / fibroblast growth factor receptor signaling pathway / signal transduction in response to DNA damage / GAB1 signalosome / 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 CSF3 (G-CSF) / 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 / EGFR Transactivation by Gastrin / Signaling by FLT3 fusion proteins / FLT3 Signaling / myelination / Signaling by FGFR1 in disease / GRB2 events in ERBB2 signaling / NCAM signaling for neurite out-growth / phosphotyrosine residue binding / ephrin receptor binding / SHC1 events in ERBB2 signaling / Downstream signal transduction / FCERI mediated Ca+2 mobilization / Constitutive Signaling by Overexpressed ERBB2 / Insulin receptor signalling cascade / InlB-mediated entry of Listeria monocytogenes into host cell / 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 / cellular response to ionizing radiation / Regulation of signaling by CBL / Negative regulation of FGFR3 signaling / FCERI mediated MAPK activation / Negative regulation of FGFR2 signaling / FCGR3A-mediated phagocytosis / Negative regulation of FGFR4 signaling / EGFR downregulation / Negative regulation of FGFR1 signaling / B cell receptor signaling pathway / Signaling by ERBB2 TMD/JMD mutants / Spry regulation of FGF signaling Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) synthetic construct (others) | |||||||||||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.8 Å | |||||||||||||||
Authors | Martin, S.F. / Clements, J.H. | |||||||||||||||
Funding support | United States, 4items
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Citation | Journal: Eur.J.Med.Chem. / Year: 2020 Title: Some thermodynamic effects of varying nonpolar surfaces in protein-ligand interactions. Authors: Cramer, D.L. / Cheng, B. / Tian, J. / Clements, J.H. / Wypych, R.M. / Martin, S.F. | |||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6wm1.cif.gz | 68 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6wm1.ent.gz | 46.7 KB | Display | PDB format |
PDBx/mmJSON format | 6wm1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wm/6wm1 ftp://data.pdbj.org/pub/pdb/validation_reports/wm/6wm1 | HTTPS FTP |
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-Related structure data
Related structure data | 6wo2C 4p9vS 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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2 |
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Unit cell |
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-Components
-Protein / Protein/peptide , 2 types, 4 molecules ACBD
#1: Protein | Mass: 13758.543 Da / Num. of mol.: 2 / Fragment: SH2 Domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GRB2, ASH / Plasmid: PQE-60 / Production host: Escherichia coli (E. coli) / Strain (production host): SG13009 / References: UniProt: P62993 #2: Protein/peptide | Mass: 643.668 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
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-Non-polymers , 4 types, 151 molecules
#3: Chemical | #4: Chemical | ChemComp-CA / | #5: Chemical | ChemComp-CL / | #6: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | 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: 2.11 Å3/Da / Density % sol: 41.77 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: An aqueous solution containing a 1.5 molar ratio of ligand to protein, 10 mg/mL, was prepared. 4.0 ul of this solution was mixed with 3.0 ul precipitant solution containing 0.1 M HEPES, pH 7. ...Details: An aqueous solution containing a 1.5 molar ratio of ligand to protein, 10 mg/mL, was prepared. 4.0 ul of this solution was mixed with 3.0 ul precipitant solution containing 0.1 M HEPES, pH 7.5, and 25% w/v polyethylene glycol, MW 10,000, and allowed to equilibrate with 350 ul of the aforementioned precipitant well solution at 298 K. Useable crystals grew after 4 weeks |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU / Wavelength: 1.5418 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: May 18, 2011 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Monochromator: Blue Max-flux Confocal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.8→51.76 Å / Num. obs: 16789 / % possible obs: 84.6 % / Redundancy: 10.2 % / Rmerge(I) obs: 0.04 / Χ2: 1.234 / Net I/σ(I): 46.7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Phasing
Phasing | Method: molecular replacement | |||||||||
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Phasing MR | Rfactor: 30.56 / Model details: Phaser MODE: MR_AUTO
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4P9V Resolution: 1.8→51.76 Å / Cor.coef. Fo:Fc: 0.96 / Cor.coef. Fo:Fc free: 0.925 / SU B: 2.888 / SU ML: 0.092 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.169 / ESU R Free: 0.166 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å | |||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 66.89 Å2 / Biso mean: 23.136 Å2 / Biso min: 7.11 Å2
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Refinement step | Cycle: final / Resolution: 1.8→51.76 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.801→1.848 Å / Rfactor Rfree error: 0
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