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Yorodumi- PDB-6mdc: Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Al... -
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-Basic information
Entry | Database: PDB / ID: 6mdc | ||||||
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Title | Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor Pyrazolo-pyrimidinone 1 SHP389 | ||||||
Components | Tyrosine-protein phosphatase non-receptor type 11 | ||||||
Keywords | HYDROLASE/HYDROLASE INHIBITOR / SHP2 / PTPN11 / PROTEIN TYROSINE PHOSPHATASE / PHOSPHATASE / ALLOSTERIC INHIBITOR / HYDROLASE-HYDROLASE INHIBITOR COMPLEX / HYDROLASE | ||||||
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 / FOURIER SYNTHESIS / Resolution: 2.14 Å | ||||||
Authors | Fodor, M. / Stams, T. | ||||||
Citation | Journal: J. Med. Chem. / Year: 2019 Title: Optimization of Fused Bicyclic Allosteric SHP2 Inhibitors. Authors: Bagdanoff, J.T. / Chen, Z. / Acker, M. / Chen, Y.N. / Chan, H. / Dore, M. / Firestone, B. / Fodor, M. / Fortanet, J. / Hentemann, M. / Kato, M. / Koenig, R. / LaBonte, L.R. / Liu, S. / ...Authors: Bagdanoff, J.T. / Chen, Z. / Acker, M. / Chen, Y.N. / Chan, H. / Dore, M. / Firestone, B. / Fodor, M. / Fortanet, J. / Hentemann, M. / Kato, M. / Koenig, R. / LaBonte, L.R. / Liu, S. / Mohseni, M. / Ntaganda, R. / Sarver, P. / Smith, T. / Sendzik, M. / Stams, T. / Spence, S. / Towler, C. / Wang, H. / Wang, P. / Williams, S.L. / LaMarche, M.J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6mdc.cif.gz | 221.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6mdc.ent.gz | 173.1 KB | Display | PDB format |
PDBx/mmJSON format | 6mdc.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6mdc_validation.pdf.gz | 1008 KB | Display | wwPDB validaton report |
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Full document | 6mdc_full_validation.pdf.gz | 1021 KB | Display | |
Data in XML | 6mdc_validation.xml.gz | 40.7 KB | Display | |
Data in CIF | 6mdc_validation.cif.gz | 60.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/md/6mdc ftp://data.pdbj.org/pub/pdb/validation_reports/md/6mdc | HTTPS FTP |
-Related 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
#1: Protein | Mass: 60335.035 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PTPN11, PTP2C, SHPTP2 / Production host: Escherichia coli (E. coli) / References: UniProt: Q06124, protein-tyrosine-phosphatase #2: Chemical | #3: Chemical | ChemComp-PO4 / #4: Water | ChemComp-HOH / | |
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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: 2.3 Å3/Da / Density % sol: 46.55 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / Details: 17% PEG3350, 200MM AMMONIUM PHOSPHATE |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Oct 14, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.14→54.06 Å / Num. obs: 58932 / % possible obs: 98.1 % / Redundancy: 3.3 % / Rmerge(I) obs: 0.133 / Net I/σ(I): 9 |
Reflection shell | Resolution: 2.14→2.15 Å / Redundancy: 3.3 % / Rmerge(I) obs: 0.866 / Mean I/σ(I) obs: 2.9 / % possible all: 99.2 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: PDB entry 2SHP2 Resolution: 2.14→21.38 Å / Cross valid method: FREE R-VALUE
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Refinement step | Cycle: LAST / Resolution: 2.14→21.38 Å
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LS refinement shell | Highest resolution: 2.14 Å / Rfactor Rfree: 0.315 / Rfactor Rwork: 0.22 |