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- PDB-6si4: p53 cancer mutant Y220S in complex with small-molecule stabilizer... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6si4 | ||||||
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Title | p53 cancer mutant Y220S in complex with small-molecule stabilizer PK9323 | ||||||
![]() | Cellular tumor antigen p53 | ||||||
![]() | DNA BINDING PROTEIN / p53 / transcription factor / tumor suppressor / cancer therapy / oncogenic mutant / protein misfolding / DNA-binding domain / druggable surface crevice / small-molecule stabilizer / mutant p53 rescue | ||||||
Function / homology | ![]() Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / signal transduction by p53 class mediator / negative regulation of G1 to G0 transition / negative regulation of glucose catabolic process to lactate via pyruvate / Transcriptional activation of cell cycle inhibitor p21 / regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Activation of NOXA and translocation to mitochondria / negative regulation of pentose-phosphate shunt / ATP-dependent DNA/DNA annealing activity ...Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / signal transduction by p53 class mediator / negative regulation of G1 to G0 transition / negative regulation of glucose catabolic process to lactate via pyruvate / Transcriptional activation of cell cycle inhibitor p21 / regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Activation of NOXA and translocation to mitochondria / negative regulation of pentose-phosphate shunt / ATP-dependent DNA/DNA annealing activity / negative regulation of helicase activity / regulation of cell cycle G2/M phase transition / intrinsic apoptotic signaling pathway in response to hypoxia / regulation of fibroblast apoptotic process / oxidative stress-induced premature senescence / oligodendrocyte apoptotic process / negative regulation of miRNA processing / positive regulation of thymocyte apoptotic process / glucose catabolic process to lactate via pyruvate / regulation of tissue remodeling / positive regulation of mitochondrial membrane permeability / negative regulation of mitophagy / positive regulation of programmed necrotic cell death / mRNA transcription / bone marrow development / circadian behavior / histone deacetylase regulator activity / germ cell nucleus / regulation of mitochondrial membrane permeability involved in apoptotic process / RUNX3 regulates CDKN1A transcription / regulation of DNA damage response, signal transduction by p53 class mediator / TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain / TP53 Regulates Transcription of Death Receptors and Ligands / Activation of PUMA and translocation to mitochondria / DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / negative regulation of glial cell proliferation / negative regulation of neuroblast proliferation / Regulation of TP53 Activity through Association with Co-factors / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / mitochondrial DNA repair / T cell lineage commitment / ER overload response / negative regulation of DNA replication / B cell lineage commitment / positive regulation of cardiac muscle cell apoptotic process / thymocyte apoptotic process / TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain / TP53 Regulates Transcription of Caspase Activators and Caspases / cardiac septum morphogenesis / positive regulation of execution phase of apoptosis / entrainment of circadian clock by photoperiod / PI5P Regulates TP53 Acetylation / Association of TriC/CCT with target proteins during biosynthesis / Zygotic genome activation (ZGA) / necroptotic process / positive regulation of release of cytochrome c from mitochondria / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / rRNA transcription / TFIID-class transcription factor complex binding / negative regulation of telomere maintenance via telomerase / SUMOylation of transcription factors / intrinsic apoptotic signaling pathway by p53 class mediator / general transcription initiation factor binding / mitophagy / Transcriptional Regulation by VENTX / DNA damage response, signal transduction by p53 class mediator / response to X-ray / replicative senescence / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / cellular response to UV-C / neuroblast proliferation / : / negative regulation of reactive oxygen species metabolic process / hematopoietic stem cell differentiation / chromosome organization / positive regulation of RNA polymerase II transcription preinitiation complex assembly / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / T cell proliferation involved in immune response / glial cell proliferation / Pyroptosis / cis-regulatory region sequence-specific DNA binding / embryonic organ development / hematopoietic progenitor cell differentiation / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / cellular response to actinomycin D / somitogenesis / type II interferon-mediated signaling pathway / cellular response to glucose starvation / core promoter sequence-specific DNA binding / negative regulation of stem cell proliferation / negative regulation of fibroblast proliferation / positive regulation of intrinsic apoptotic signaling pathway / gastrulation / MDM2/MDM4 family protein binding / cardiac muscle cell apoptotic process / mitotic G1 DNA damage checkpoint signaling / 14-3-3 protein binding / Regulation of TP53 Activity through Acetylation / tumor necrosis factor-mediated signaling pathway / response to salt stress Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Joerger, A.C. / Kraemer, A. / Knapp, S. / Structural Genomics Consortium (SGC) | ||||||
Funding support | ![]()
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![]() | ![]() Title: Targeting Cavity-Creating p53 Cancer Mutations with Small-Molecule Stabilizers: the Y220X Paradigm. Authors: Bauer, M.R. / Kramer, A. / Settanni, G. / Jones, R.N. / Ni, X. / Khan Tareque, R. / Fersht, A.R. / Spencer, J. / Joerger, A.C. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 103 KB | Display | ![]() |
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PDB format | ![]() | 76.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 6shzC ![]() 6si0C ![]() 6si1C ![]() 6si2C ![]() 6si3C ![]() 2j1xS S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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2 | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 24514.746 Da / Num. of mol.: 2 / Fragment: DNA-binding domain / Mutation: M133L, V203A, Y220S, N239Y, N268D Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Chemical | #3: Chemical | #4: Chemical | ChemComp-GOL / | #5: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.49 Å3/Da / Density % sol: 50.6 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop Details: Protein solution: 6 mg/ml protein in 25 mM sodium phosphate, ph 7.2, 150 mm KCl, 5 mm DTT. Reservoir buffer: 100 mm HEPES, pH 7.2, 19% (w/v) polyethylene glycol 4000, 5 mm DTT, 2 mM PK9323. |
-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: Sep 3, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.999998 Å / Relative weight: 1 |
Reflection | Resolution: 1.8→48.09 Å / Num. obs: 45643 / % possible obs: 99.1 % / Redundancy: 4.3 % / Biso Wilson estimate: 19.47 Å2 / CC1/2: 0.996 / Rmerge(I) obs: 0.089 / Rpim(I) all: 0.048 / Rrim(I) all: 0.101 / Net I/σ(I): 8.9 / Num. measured all: 198228 |
Reflection shell | Resolution: 1.8→1.84 Å / Redundancy: 4.4 % / Rmerge(I) obs: 0.541 / Mean I/σ(I) obs: 2.5 / Num. unique obs: 2709 / CC1/2: 0.873 / Rpim(I) all: 0.286 / Rrim(I) all: 0.615 / % possible all: 99.9 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 2J1X Resolution: 1.8→42.295 Å / SU ML: 0.2 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 25.32 / 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: 63.07 Å2 / Biso mean: 22.532 Å2 / Biso min: 8.79 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.8→42.295 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0
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