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Open data
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Basic information
Entry | Database: PDB / ID: 8a6f | ||||||
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Title | Small molecule stabilizer (compound 8) for C-RAF and 14-3-3 | ||||||
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![]() | STRUCTURAL PROTEIN / 14-3-3 / C-RAF / Stabilization | ||||||
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 | ![]() ![]() ![]() | ||||||
![]() | 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 | ![]() | 113.8 KB | Display | ![]() |
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PDB format | ![]() | 86.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 8a62C ![]() 8a65C ![]() 8a68C ![]() 8a6hC ![]() 8admC ![]() 8afnC ![]() 8av0C ![]() 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: 1206.183 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() References: UniProt: P04049, non-specific serine/threonine protein kinase |
-Non-polymers , 4 types, 336 molecules ![](data/chem/img/CL.gif)
![](data/chem/img/MG.gif)
![](data/chem/img/O56.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/MG.gif)
![](data/chem/img/O56.gif)
![](data/chem/img/HOH.gif)
#3: Chemical | ChemComp-CL / | ||||
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#4: Chemical | #5: Chemical | ChemComp-O56 / | #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: 2.65 Å3/Da / Density % sol: 53.57 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop Details: 0.095 M HEPES pH 7.5, 0.19 M CaCl2, 26% (v/v) PEG 400 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: 1.0332 Å / Relative weight: 1 |
Reflection | Resolution: 1.6→45.77 Å / Num. obs: 507054 / % possible obs: 100 % / Redundancy: 12.9 % / CC1/2: 0.996 / Net I/σ(I): 14.6 |
Reflection shell | Resolution: 1.6→1.63 Å / Num. unique obs: 1906 / CC1/2: 0.437 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 3iqu Resolution: 1.6→45.77 Å / SU ML: 0.15 / Cross valid method: THROUGHOUT / σ(F): 1.33 / Phase error: 18.45 / Stereochemistry target values: ML
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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 max: 98.06 Å2 / Biso mean: 23.7068 Å2 / Biso min: 7.29 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.6→45.77 Å
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 27
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