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- PDB-8ats: Small molecular stabilizer for C-RAF (pS259) and 14-3-3 (1075306) -
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Open data
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Basic information
Entry | Database: PDB / ID: 8ats | ||||||
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Title | Small molecular stabilizer for C-RAF (pS259) and 14-3-3 (1075306) | ||||||
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![]() | STRUCTURAL PROTEIN / 14-3-3 / ERalpha / stabilization / covalent | ||||||
Function / homology | ![]() death-inducing signaling complex assembly / intermediate filament cytoskeleton organization / type B pancreatic cell proliferation / regulation of Rho protein signal transduction / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / Rap1 signalling / regulation of cell motility / insulin secretion involved in cellular response to glucose stimulus / Negative feedback regulation of MAPK pathway ...death-inducing signaling complex assembly / intermediate filament cytoskeleton organization / type B pancreatic cell proliferation / regulation of Rho protein signal transduction / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / Rap1 signalling / regulation of cell motility / insulin secretion involved in cellular response to glucose stimulus / Negative feedback regulation of MAPK pathway / GP1b-IX-V activation signalling / IFNG signaling activates MAPKs / regulation of epidermal cell division / protein kinase C inhibitor activity / ERBB2-ERBB3 signaling pathway / regulation of cell differentiation / positive regulation of epidermal cell differentiation / keratinocyte development / keratinization / face development / pseudopodium / somatic stem cell population maintenance / thyroid gland development / neurotrophin TRK receptor signaling pathway / Regulation of localization of FOXO transcription factors / keratinocyte proliferation / phosphoserine residue binding / extrinsic apoptotic signaling pathway via death domain receptors / MAP kinase kinase kinase activity / Activation of BAD and translocation to mitochondria / negative regulation of keratinocyte proliferation / establishment of skin barrier / negative regulation of protein-containing complex assembly / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / Schwann cell development / type II interferon-mediated signaling pathway / activation of adenylate cyclase activity / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / negative regulation of stem cell proliferation / RHO GTPases activate PKNs / protein sequestering activity / protein kinase A signaling / response to muscle stretch / negative regulation of innate immune response / myelination / protein export from nucleus / CD209 (DC-SIGN) signaling / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / insulin-like growth factor receptor signaling pathway / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / release of cytochrome c from mitochondria / positive regulation of protein export from nucleus / thymus development / stem cell proliferation / Translocation of SLC2A4 (GLUT4) to the plasma membrane / TP53 Regulates Metabolic Genes / RAF activation / negative regulation of protein kinase activity / wound healing / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / Stimuli-sensing channels / Negative regulation of MAPK pathway / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / intrinsic apoptotic signaling pathway in response to DNA damage / MAPK cascade / Signaling by BRAF and RAF1 fusions / protein localization / insulin receptor signaling pathway / positive regulation of peptidyl-serine phosphorylation / positive regulation of cell growth / regulation of apoptotic process / mitochondrial outer membrane / positive regulation of MAPK cascade / regulation of cell cycle / non-specific serine/threonine protein kinase / protein kinase activity / cadherin binding / negative regulation of cell population proliferation / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / negative regulation of apoptotic process / apoptotic process / protein kinase binding / Golgi apparatus / negative regulation of transcription by RNA polymerase II / enzyme binding / signal transduction / positive regulation of transcription by RNA polymerase II / mitochondrion / extracellular space / extracellular exosome / ATP binding / identical protein binding Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Visser, E.J. / Overmans, M.J.A.M. / Vandenboorn, E.M.F. / Ottmann, C. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Structure-Based Optimization of Covalent, Small-Molecule Stabilizers of the 14-3-3 sigma /ER alpha Protein-Protein Interaction from Nonselective Fragments. Authors: Konstantinidou, M. / Visser, E.J. / Vandenboorn, E. / Chen, S. / Jaishankar, P. / Overmans, M. / Dutta, S. / Neitz, R.J. / Renslo, A.R. / Ottmann, C. / Brunsveld, L. / Arkin, M.R. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 121.7 KB | Display | ![]() |
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PDB format | ![]() | 91.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 8ai0C ![]() 8alrC ![]() 8altC ![]() 8alvC ![]() 8alwC ![]() 8am7C ![]() 8anfC ![]() 8aoyC ![]() 8apsC ![]() 8aq1C ![]() 8aqcC ![]() 8aqeC ![]() 8aqzC ![]() 8ar4C ![]() 8ar5C ![]() 8argC ![]() 8aroC ![]() 8arqC ![]() 8arrC ![]() 8arwC ![]() 8arxC ![]() 8aryC ![]() 8arzC ![]() 8as1C ![]() 8at9C ![]() 8atpC ![]() 8atrC ![]() 8au2C ![]() 8ausC ![]() 8auyC ![]() 8av3C ![]() 8av4C ![]() 8av7C ![]() 8av8C ![]() 8awgC ![]() 8axeC ![]() 8axuC ![]() 8azeC ![]() 8b39C ![]() 3iquS S: Starting model for refinement C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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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 / Protein/peptide , 2 types, 2 molecules AP
#1: Protein | Mass: 26542.914 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein/peptide | Mass: 1070.028 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() References: UniProt: P04049, non-specific serine/threonine protein kinase |
-Non-polymers , 4 types, 188 molecules ![](data/chem/img/CL.gif)
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![](data/chem/img/HOH.gif)
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#3: Chemical | ChemComp-CL / | ||||
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#4: Chemical | #5: Chemical | ChemComp-O5I / | #6: Water | ChemComp-HOH / | |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.6 Å3/Da / Density % sol: 52.66 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop Details: 0.095 M HEPES (pH 7.1), PEG400 (24% (v/v)), 0.19 M CaCl2 and 5% (v/v) Glycerol |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Nov 4, 2021 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.03322 Å / Relative weight: 1 |
Reflection | Resolution: 1.4→45.46 Å / Num. obs: 56825 / % possible obs: 99.8 % / Redundancy: 1.9 % / CC1/2: 1 / Net I/σ(I): 25.2 |
Reflection shell | Resolution: 1.4→1.42 Å / Num. unique obs: 2721 / CC1/2: 0.889 |
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Processing
Software |
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Refinement | Method to determine structure: ![]() Starting model: 3iqu Resolution: 1.4→45.46 Å / Cor.coef. Fo:Fc: 0.97 / Cor.coef. Fo:Fc free: 0.968 / SU B: 1.57 / SU ML: 0.028 / Cross valid method: THROUGHOUT / ESU R: 0.052 / ESU R Free: 0.048 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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Solvent computation | Ion probe radii: 0.7 Å / Shrinkage radii: 0.7 Å / VDW probe radii: 1.1 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 22.614 Å2
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Refinement step | Cycle: LAST / Resolution: 1.4→45.46 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.4→1.436 Å / Total num. of bins used: 20
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