+Open data
-Basic information
Entry | Database: PDB / ID: 6si1 | ||||||
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Title | p53 cancer mutant Y220H | ||||||
Components | Cellular tumor antigen p53 | ||||||
Keywords | DNA BINDING PROTEIN / p53 / transcription factor / tumor suppressor / cancer therapy / oncogenic mutant / protein misfolding / DNA-binding domain / mutant p53 rescue / Structural Genomics / Structural Genomics Consortium / SGC | ||||||
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 / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / negative regulation of neuroblast proliferation / Regulation of TP53 Activity through Association with Co-factors / mitochondrial DNA repair / T cell lineage commitment / negative regulation of DNA replication / ER overload response / 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 / TFIID-class transcription factor complex binding / rRNA transcription / mitophagy / SUMOylation of transcription factors / negative regulation of telomere maintenance via telomerase / intrinsic apoptotic signaling pathway by p53 class mediator / general transcription initiation factor binding / 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 / : / hematopoietic stem cell differentiation / negative regulation of reactive oxygen species metabolic process / chromosome organization / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / T cell proliferation involved in immune response / glial cell proliferation / embryonic organ development / positive regulation of RNA polymerase II transcription preinitiation complex assembly / Pyroptosis / cis-regulatory region sequence-specific DNA binding / hematopoietic progenitor cell differentiation / cellular response to glucose starvation / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / cellular response to actinomycin D / somitogenesis / type II interferon-mediated signaling pathway / negative regulation of stem cell proliferation / core promoter sequence-specific DNA binding / positive regulation of intrinsic apoptotic signaling pathway / negative regulation of fibroblast proliferation / gastrulation / MDM2/MDM4 family protein binding / cardiac muscle cell apoptotic process / transcription initiation-coupled chromatin remodeling / 14-3-3 protein binding / mitotic G1 DNA damage checkpoint signaling / Regulation of TP53 Activity through Acetylation / response to salt stress Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 1.44 Å | ||||||
Authors | Joerger, A.C. / Kraemer, A. / Knapp, S. / Structural Genomics Consortium (SGC) | ||||||
Funding support | Germany, 1items
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Citation | Journal: Acs Chem.Biol. / Year: 2020 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: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6si1.cif.gz | 183.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6si1.ent.gz | 143.5 KB | Display | PDB format |
PDBx/mmJSON format | 6si1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6si1_validation.pdf.gz | 461 KB | Display | wwPDB validaton report |
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Full document | 6si1_full_validation.pdf.gz | 463.4 KB | Display | |
Data in XML | 6si1_validation.xml.gz | 21.8 KB | Display | |
Data in CIF | 6si1_validation.cif.gz | 33 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/si/6si1 ftp://data.pdbj.org/pub/pdb/validation_reports/si/6si1 | HTTPS FTP |
-Related structure data
Related structure data | 6shzC 6si0C 6si2C 6si3C 6si4C 2j1xS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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2 |
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Unit cell |
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-Components
-Protein , 1 types, 2 molecules AB
#1: Protein | Mass: 24565.814 Da / Num. of mol.: 2 / Fragment: DNA-binding domain / Mutation: M133L, V203A, Y220H, N239Y, N268D Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TP53, P53 / Production host: Escherichia coli (E. coli) / References: UniProt: P04637 |
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-Non-polymers , 5 types, 522 molecules
#2: Chemical | #3: Chemical | ChemComp-EDO / | #4: Chemical | #5: Chemical | ChemComp-EPE / | #6: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | N |
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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: 2.45 Å3/Da / Density % sol: 49.71 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7.2 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. |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1.000031 Å |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jun 30, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.000031 Å / Relative weight: 1 |
Reflection | Resolution: 1.44→47.78 Å / Num. obs: 86307 / % possible obs: 98.5 % / Redundancy: 5.5 % / Biso Wilson estimate: 13.45 Å2 / CC1/2: 0.995 / Rmerge(I) obs: 0.086 / Rpim(I) all: 0.039 / Rrim(I) all: 0.095 / Net I/σ(I): 9.3 / Num. measured all: 478157 / Scaling rejects: 53 |
Reflection shell | Resolution: 1.44→1.47 Å / Redundancy: 5.6 % / Rmerge(I) obs: 0.635 / Mean I/σ(I) obs: 2.4 / Num. unique obs: 4333 / CC1/2: 0.888 / Rpim(I) all: 0.287 / Rrim(I) all: 0.698 / % possible all: 97.7 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: 2J1X Resolution: 1.44→47.777 Å / SU ML: 0.14 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 17.68 / 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: 56.32 Å2 / Biso mean: 18.7892 Å2 / Biso min: 8.06 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.44→47.777 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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