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Yorodumi- PDB-6cmr: Closed structure of active SHP2 mutant E76D bound to SHP099 inhibitor -
+Open data
-Basic information
Entry | Database: PDB / ID: 6cmr | ||||||||||||
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Title | Closed structure of active SHP2 mutant E76D bound to SHP099 inhibitor | ||||||||||||
Components | Tyrosine-protein phosphatase non-receptor type 11 | ||||||||||||
Keywords | HYDROLASE/HYDROLASE Inhibitor / protein tyrosine phosphatase / src homology domain 2 / inactive state / active mutant / HYDROLASE / HYDROLASE-HYDROLASE Inhibitor complex | ||||||||||||
Function / homology | Function and homology information negative regulation of cortisol secretion / intestinal epithelial cell migration / microvillus organization / negative regulation of growth hormone secretion / genitalia development / atrioventricular canal development / negative regulation of cell adhesion mediated by integrin / STAT5 Activation / Netrin mediated repulsion signals / positive regulation of hormone secretion ...negative regulation of cortisol secretion / intestinal epithelial cell migration / microvillus organization / negative regulation of growth hormone secretion / genitalia development / atrioventricular canal development / negative regulation of cell adhesion mediated by integrin / STAT5 Activation / Netrin mediated repulsion signals / positive regulation of hormone secretion / cerebellar cortex formation / multicellular organismal reproductive process / regulation of protein export from nucleus / positive regulation of ossification / hormone metabolic process / Interleukin-37 signaling / Signaling by Leptin / negative regulation of chondrocyte differentiation / MET activates PTPN11 / Regulation of RUNX1 Expression and Activity / face morphogenesis / ERBB signaling pathway / Costimulation by the CD28 family / Signal regulatory protein family interactions / peptide hormone receptor binding / negative regulation of type I interferon production / platelet formation / megakaryocyte development / organ growth / CTLA4 inhibitory signaling / triglyceride metabolic process / Platelet sensitization by LDL / Interleukin-20 family signaling / PI-3K cascade:FGFR3 / Interleukin-6 signaling / STAT5 activation downstream of FLT3 ITD mutants / PI-3K cascade:FGFR2 / PI-3K cascade:FGFR4 / Prolactin receptor signaling / PI-3K cascade:FGFR1 / MAPK3 (ERK1) activation / PECAM1 interactions / MAPK1 (ERK2) activation / regulation of cell adhesion mediated by integrin / regulation of type I interferon-mediated signaling pathway / Bergmann glial cell differentiation / phosphoprotein phosphatase activity / inner ear development / neurotrophin TRK receptor signaling pathway / platelet-derived growth factor receptor signaling pathway / non-membrane spanning protein tyrosine phosphatase activity / RET signaling / peptidyl-tyrosine dephosphorylation / Interleukin-3, Interleukin-5 and GM-CSF signaling / Regulation of IFNA/IFNB signaling / PI3K Cascade / PD-1 signaling / regulation of protein-containing complex assembly / ephrin receptor signaling pathway / fibroblast growth factor receptor signaling pathway / GAB1 signalosome / Activated NTRK2 signals through FRS2 and FRS3 / negative regulation of insulin secretion / Regulation of IFNG signaling / positive regulation of insulin receptor signaling pathway / FRS-mediated FGFR3 signaling / Signaling by CSF3 (G-CSF) / Signaling by FLT3 ITD and TKD mutants / homeostasis of number of cells within a tissue / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / Tie2 Signaling / FRS-mediated FGFR1 signaling / cellular response to epidermal growth factor stimulus / cell adhesion molecule binding / GPVI-mediated activation cascade / T cell costimulation / FLT3 Signaling / positive regulation of interferon-beta production / hormone-mediated signaling pathway / phosphotyrosine residue binding / positive regulation of mitotic cell cycle / Downstream signal transduction / protein dephosphorylation / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / protein-tyrosine-phosphatase / axonogenesis / protein tyrosine kinase binding / DNA damage checkpoint signaling / protein tyrosine phosphatase activity / integrin-mediated signaling pathway / positive regulation of glucose import / Negative regulation of FGFR3 signaling / Negative regulation of FGFR2 signaling / Negative regulation of FGFR4 signaling / Negative regulation of FGFR1 signaling / Spry regulation of FGF signaling / insulin receptor binding / epidermal growth factor receptor signaling pathway / multicellular organism growth Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.21 Å | ||||||||||||
Authors | Padua, R.A.P. / Sun, Y. / Marko, I. / Pitsawong, W. / Kern, D. | ||||||||||||
Funding support | Brazil, United States, 3items
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Citation | Journal: Nat Commun / Year: 2018 Title: Mechanism of activating mutations and allosteric drug inhibition of the phosphatase SHP2. Authors: Padua, R.A.P. / Sun, Y. / Marko, I. / Pitsawong, W. / Stiller, J.B. / Otten, R. / Kern, D. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6cmr.cif.gz | 348 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6cmr.ent.gz | 237 KB | Display | PDB format |
PDBx/mmJSON format | 6cmr.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6cmr_validation.pdf.gz | 700.2 KB | Display | wwPDB validaton report |
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Full document | 6cmr_full_validation.pdf.gz | 700.9 KB | Display | |
Data in XML | 6cmr_validation.xml.gz | 19.2 KB | Display | |
Data in CIF | 6cmr_validation.cif.gz | 26.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cm/6cmr ftp://data.pdbj.org/pub/pdb/validation_reports/cm/6cmr | HTTPS FTP |
-Related structure data
Related structure data | 6cmpC 6cmqC 6cmsC 4dgpS 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
#1: Protein | Mass: 60990.789 Da / Num. of mol.: 1 / Mutation: E76D Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PTPN11, PTP2C, SHPTP2 / Plasmid: pET28a / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: Q06124, protein-tyrosine-phosphatase |
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#2: Chemical | ChemComp-5OD / |
#3: 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: 2.17 Å3/Da / Density % sol: 43.19 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, sitting drop Details: 15% PEG 20,000 and 10 mM potassium hydrogen tartrate |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 8.2.2 / Wavelength: 0.99997 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Dec 14, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.99997 Å / Relative weight: 1 |
Reflection | Resolution: 2.21→52.79 Å / Num. obs: 25969 / % possible obs: 99.92 % / Redundancy: 6.1 % / Biso Wilson estimate: 44.34 Å2 / CC1/2: 0.993 / Rmerge(I) obs: 0.1645 / Rpim(I) all: 0.07346 / Net I/σ(I): 5.85 |
Reflection shell | Resolution: 2.21→2.289 Å / Redundancy: 6.6 % / Num. unique obs: 2566 / Rpim(I) all: 0.7128 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4DGP Resolution: 2.21→52.79 Å / SU ML: 0.3859 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 29.2629 / Stereochemistry target values: GeoStd + Monomer Library
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 58.13 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.21→52.79 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION
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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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