+Open data
-Basic information
Entry | Database: PDB / ID: 8qwl | ||||||
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Title | Structure of p53 cancer mutant Y163C | ||||||
Components | Cellular tumor antigen p53 | ||||||
Keywords | DNA BINDING PROTEIN / tumor suppressor / transcription factor / cancer mutation / protein stability / conformational mutant | ||||||
Function / homology | Function and homology information 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 / neuroblast proliferation / cellular response to UV-C / : / 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 / response to salt stress / tumor necrosis factor-mediated signaling pathway Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.65 Å | ||||||
Authors | Balourdas, D.I. / Markl, A.M. / Kraemer, A. / Knapp, S. / Joerger, A.C. / Structural Genomics Consortium (SGC) | ||||||
Funding support | Germany, 1items
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Citation | Journal: Cell Death Dis / Year: 2024 Title: Structural basis of p53 inactivation by cavity-creating cancer mutations and its implications for the development of mutant p53 reactivators. Authors: Balourdas, D.I. / Markl, A.M. / Kramer, A. / Settanni, G. / Joerger, A.C. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8qwl.cif.gz | 70.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8qwl.ent.gz | 40.5 KB | Display | PDB format |
PDBx/mmJSON format | 8qwl.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qw/8qwl ftp://data.pdbj.org/pub/pdb/validation_reports/qw/8qwl | HTTPS FTP |
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-Related structure data
Related structure data | 8qwkC 8qwmC 8qwnC 8qwoC 8qwpC 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
#1: Protein | Mass: 24530.811 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TP53 / Production host: Escherichia coli (E. coli) / References: UniProt: P04637 | ||||||
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#2: Chemical | ChemComp-ZN / | ||||||
#3: Chemical | #4: Chemical | ChemComp-MLI / | #5: Water | ChemComp-HOH / | Has ligand of interest | N | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 1.95 Å3/Da / Density % sol: 36.77 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop Details: Protein solution: 5.5-6.0 mg/ml in 25 mM HEPES (pH 7.5), 200 mM NaCl, 0.5 mM TCEP. Reservoir buffer: 24% PEG 3350 (w/v), 10% ethylene glycol (v/v), 0.2 M sodium malonate (pH 7.0). |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 0.9999 Å |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Dec 18, 2020 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9999 Å / Relative weight: 1 |
Reflection | Resolution: 1.65→42.3 Å / Num. obs: 23257 / % possible obs: 99.6 % / Redundancy: 5.5 % / Biso Wilson estimate: 18.3638057837 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.069 / Net I/σ(I): 13.1 |
Reflection shell | Resolution: 1.65→1.68 Å / Redundancy: 4 % / Rmerge(I) obs: 0.666 / Mean I/σ(I) obs: 2 / Num. unique obs: 1107 / CC1/2: 0.815 / % possible all: 98.7 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.65→42.25 Å / SU ML: 0.180518872237 / Cross valid method: FREE R-VALUE / σ(F): 1.34748774091 / Phase error: 21.1762754958 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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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 mean: 23.9119550256 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.65→42.25 Å
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Refine LS restraints |
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LS refinement shell |
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