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Open data
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Basic information
Entry | Database: PDB / ID: 8a65 | ||||||
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Title | Small molecule stabilizer (compound 3) for FOXO1 and 14-3-3 | ||||||
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![]() | STRUCTURAL PROTEIN / 14-3-3 / FOXO1 / Stabilization | ||||||
Function / homology | ![]() cellular response to hyperoxia / regulation of transcription initiation by RNA polymerase II / AKT-mediated inactivation of FOXO1A / FOXO-mediated transcription of cell cycle genes / AKT phosphorylates targets in the nucleus / positive regulation of smooth muscle cell apoptotic process / neuronal stem cell population maintenance / regulation of neural precursor cell proliferation / response to fatty acid / Regulation of FOXO transcriptional activity by acetylation ...cellular response to hyperoxia / regulation of transcription initiation by RNA polymerase II / AKT-mediated inactivation of FOXO1A / FOXO-mediated transcription of cell cycle genes / AKT phosphorylates targets in the nucleus / positive regulation of smooth muscle cell apoptotic process / neuronal stem cell population maintenance / regulation of neural precursor cell proliferation / response to fatty acid / Regulation of FOXO transcriptional activity by acetylation / regulation of reactive oxygen species metabolic process / negative regulation of stress-activated MAPK cascade / negative regulation of cardiac muscle hypertrophy in response to stress / cellular response to cold / FOXO-mediated transcription of cell death genes / temperature homeostasis / negative regulation of fat cell differentiation / protein acetylation / regulation of epidermal cell division / protein kinase C inhibitor activity / positive regulation of epidermal cell differentiation / blood vessel development / keratinocyte development / fat cell differentiation / keratinization / Constitutive Signaling by AKT1 E17K in Cancer / intracellular glucose homeostasis / Regulation of gene expression in beta cells / Regulation of localization of FOXO transcription factors / keratinocyte proliferation / phosphoserine residue binding / Activation of BAD and translocation to mitochondria / cellular response to nitric oxide / negative regulation of keratinocyte proliferation / canonical Wnt signaling pathway / establishment of skin barrier / negative regulation of insulin secretion / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / positive regulation of autophagy / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / energy homeostasis / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / negative regulation of stem cell proliferation / RHO GTPases activate PKNs / positive regulation of gluconeogenesis / protein kinase A signaling / protein sequestering activity / negative regulation of innate immune response / protein export from nucleus / cellular response to starvation / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / positive regulation of protein export from nucleus / release of cytochrome c from mitochondria / protein phosphatase 2A binding / stem cell proliferation / Translocation of SLC2A4 (GLUT4) to the plasma membrane / promoter-specific chromatin binding / TP53 Regulates Metabolic Genes / negative regulation of protein kinase activity / MAPK6/MAPK4 signaling / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / negative regulation of canonical Wnt signaling pathway / chromatin DNA binding / beta-catenin binding / autophagy / DNA-binding transcription repressor activity, RNA polymerase II-specific / positive regulation of protein catabolic process / cellular response to insulin stimulus / intrinsic apoptotic signaling pathway in response to DNA damage / insulin receptor signaling pathway / gene expression / cellular response to oxidative stress / positive regulation of cell growth / DNA-binding transcription activator activity, RNA polymerase II-specific / Interleukin-4 and Interleukin-13 signaling / sequence-specific DNA binding / nucleic acid binding / DNA-binding transcription factor activity, RNA polymerase II-specific / regulation of cell cycle / cadherin binding / positive regulation of apoptotic process / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / negative regulation of DNA-templated transcription / apoptotic process / ubiquitin protein ligase binding / DNA damage response / chromatin binding / chromatin / regulation of transcription by RNA polymerase II / negative regulation of apoptotic process / protein kinase binding / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / signal transduction / positive regulation of transcription by RNA polymerase II / mitochondrion / extracellular space / extracellular exosome Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Kenanova, D.N. / Visser, E.J. / Virta, J. / Sijbesma, E. / Centorrino, F. / Zhong, M. / Vickery, H. / Neitz, J. / Brunsveld, L. / Ottmann, C. / Arkin, M.R. | ||||||
Funding support | ![]()
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![]() | ![]() Title: A Systematic Approach to the Discovery of Protein-Protein Interaction Stabilizers. Authors: Kenanova, D.N. / Visser, E.J. / Virta, J.M. / Sijbesma, E. / Centorrino, F. / Vickery, H.R. / Zhong, M. / Neitz, R.J. / Brunsveld, L. / Ottmann, C. / 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 | ![]() | 72.8 KB | Display | ![]() |
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PDB format | ![]() | 50.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 789.6 KB | Display | ![]() |
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Full document | ![]() | 793.2 KB | Display | |
Data in XML | ![]() | 15.2 KB | Display | |
Data in CIF | ![]() | 22.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8a62C ![]() 8a68C ![]() 8a6fC ![]() 8a6hC ![]() 8admC ![]() 8afnC ![]() 8av0C ![]() 4jc3S 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
#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: 1136.090 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() | ||||||
#3: Chemical | #4: Chemical | ChemComp-L70 / ( | #5: Water | ChemComp-HOH / | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.6 Å3/Da / Density % sol: 52.64 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop Details: 0.095 M HEPES pH 7.3, 0.19 M CaCl2, 5% glycerol, 25% PEG 400 |
-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 11, 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: 1.6→45.47 Å / Num. obs: 518652 / % possible obs: 100 % / Redundancy: 13.5 % / CC1/2: 1 / Net I/σ(I): 55.7 |
Reflection shell | Resolution: 1.6→1.63 Å / Num. unique obs: 1881 / CC1/2: 0.997 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 4JC3 Resolution: 1.6→45.47 Å / Cor.coef. Fo:Fc: 0.961 / Cor.coef. Fo:Fc free: 0.948 / SU B: 1.142 / SU ML: 0.042 / Cross valid method: THROUGHOUT / ESU R: 0.078 / ESU R Free: 0.078 / 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: 0.9 Å / Shrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 18.161 Å2
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Refinement step | Cycle: LAST / Resolution: 1.6→45.47 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.6→1.642 Å / Total num. of bins used: 20
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