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Yorodumi- PDB-8atr: Small molecular stabilizer for C-RAF (pS259) and 14-3-3 (1075297) -
+Open data
-Basic information
Entry | Database: PDB / ID: 8atr | ||||||
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Title | Small molecular stabilizer for C-RAF (pS259) and 14-3-3 (1075297) | ||||||
Components |
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Keywords | STRUCTURAL PROTEIN / 14-3-3 / ERalpha / stabilization / 1080272 / covalent | ||||||
Function / homology | Function and homology information 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 / IFNG signaling activates MAPKs / GP1b-IX-V activation signalling / ERBB2-ERBB3 signaling pathway / regulation of epidermal cell division / protein kinase C inhibitor activity / positive regulation of epidermal cell differentiation / keratinocyte development / keratinization / regulation of cell differentiation / 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 / extrinsic apoptotic signaling pathway via death domain receptors / phosphoserine residue binding / 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 / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / negative regulation of stem cell proliferation / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / RHO GTPases activate PKNs / protein kinase A signaling / protein sequestering activity / activation of adenylate cyclase activity / response to muscle stretch / negative regulation of innate immune response / myelination / protein export from nucleus / CD209 (DC-SIGN) signaling / insulin-like growth factor receptor signaling pathway / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / positive regulation of protein export from nucleus / release of cytochrome c from mitochondria / 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 / Signaling by high-kinase activity BRAF mutants / wound healing / MAP2K and MAPK activation / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / 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 / insulin receptor signaling pathway / positive regulation of peptidyl-serine phosphorylation / positive regulation of cell growth / regulation of apoptotic process / mitochondrial outer membrane / Ras protein signal transduction / positive regulation of MAPK cascade / non-specific serine/threonine protein kinase / regulation of cell cycle / protein kinase activity / cadherin binding / negative regulation of cell population proliferation / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / apoptotic process / negative regulation of apoptotic process / protein kinase binding / Golgi apparatus / enzyme binding / negative regulation of transcription by RNA polymerase II / 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 | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.7 Å | ||||||
Authors | Visser, E.J. / Overmans, M.J.A.M. / Vandenboorn, E.M.F. / Ottmann, C. | ||||||
Funding support | Netherlands, 1items
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Citation | Journal: J.Am.Chem.Soc. / Year: 2023 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: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8atr.cif.gz | 72.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8atr.ent.gz | 50 KB | Display | PDB format |
PDBx/mmJSON format | 8atr.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8atr_validation.pdf.gz | 723.1 KB | Display | wwPDB validaton report |
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Full document | 8atr_full_validation.pdf.gz | 724 KB | Display | |
Data in XML | 8atr_validation.xml.gz | 13.8 KB | Display | |
Data in CIF | 8atr_validation.cif.gz | 20.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/at/8atr ftp://data.pdbj.org/pub/pdb/validation_reports/at/8atr | HTTPS FTP |
-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 8atsC 8au2C 8ausC 8auyC 8av3C 8av4C 8av7C 8av8C 8awgC 8axeC 8axuC 8azeC 8b39C 3iquS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-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.) Homo sapiens (human) / Gene: SFN, HME1 / Production host: Escherichia coli (E. coli) / References: UniProt: P31947 |
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#2: Protein/peptide | Mass: 1070.028 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) References: UniProt: P04049, non-specific serine/threonine protein kinase |
-Non-polymers , 4 types, 271 molecules
#3: Chemical | ChemComp-CL / | ||||
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#4: Chemical | #5: Chemical | ChemComp-O6L / | #6: Water | ChemComp-HOH / | |
-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: 2.7 Å3/Da / Density % sol: 54.38 % |
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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: SYNCHROTRON / Site: ESRF / Beamline: ID23-2 / Wavelength: 0.87313 Å |
Detector | Type: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Jan 29, 2022 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.87313 Å / Relative weight: 1 |
Reflection | Resolution: 1.7→42.23 Å / Num. obs: 33236 / % possible obs: 100 % / Redundancy: 1.9 % / CC1/2: 0.998 / Net I/σ(I): 13.1 |
Reflection shell | Resolution: 1.7→1.73 Å / Num. unique obs: 1755 / CC1/2: 0.93 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3iqu Resolution: 1.7→42.23 Å / Cor.coef. Fo:Fc: 0.951 / Cor.coef. Fo:Fc free: 0.941 / SU B: 1.867 / SU ML: 0.063 / Cross valid method: THROUGHOUT / ESU R: 0.101 / ESU R Free: 0.097 / 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: 1 Å / Shrinkage radii: 1 Å / VDW probe radii: 1.5 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 17.91 Å2
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Refinement step | Cycle: LAST / Resolution: 1.7→42.23 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.7→1.744 Å / Total num. of bins used: 20
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