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- PDB-8qwk: Structure of p53 cancer mutant Y126C -

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Basic information

Entry
Database: PDB / ID: 8qwk
TitleStructure of p53 cancer mutant Y126C
ComponentsCellular tumor antigen p53
KeywordsDNA 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 / RUNX3 regulates CDKN1A transcription / germ cell nucleus / regulation of mitochondrial membrane permeability involved in apoptotic process / 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 / rRNA transcription / TFIID-class transcription factor complex binding / 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 / T cell proliferation involved in immune response / negative regulation of reactive oxygen species metabolic process / chromosome organization / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / 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 / cellular response to actinomycin D / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / somitogenesis / type II interferon-mediated signaling pathway / positive regulation of intrinsic apoptotic signaling pathway / core promoter sequence-specific DNA binding / negative regulation of stem cell proliferation / 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
Cellular tumor antigen p53, transactivation domain 2 / Transactivation domain 2 / p53 transactivation domain / P53 transactivation motif / p53 family signature. / p53, tetramerisation domain / P53 tetramerisation motif / p53, DNA-binding domain / P53 DNA-binding domain / p53 tumour suppressor family ...Cellular tumor antigen p53, transactivation domain 2 / Transactivation domain 2 / p53 transactivation domain / P53 transactivation motif / p53 family signature. / p53, tetramerisation domain / P53 tetramerisation motif / p53, DNA-binding domain / P53 DNA-binding domain / p53 tumour suppressor family / p53-like tetramerisation domain superfamily / p53/RUNT-type transcription factor, DNA-binding domain superfamily / p53-like transcription factor, DNA-binding
Similarity search - Domain/homology
Cellular tumor antigen p53
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.69 Å
AuthorsMarkl, A.M. / Balourdas, D.I. / Kraemer, A. / Knapp, S. / Joerger, A.C. / Structural Genomics Consortium (SGC)
Funding support Germany, 1items
OrganizationGrant numberCountry
German Research Foundation (DFG)JO 1473/1-3 Germany
CitationJournal: 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
DepositionOct 19, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jun 19, 2024Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Cellular tumor antigen p53
hetero molecules


Theoretical massNumber of molelcules
Total (without water)24,6583
Polymers24,5311
Non-polymers1272
Water2,630146
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area170 Å2
ΔGint2 kcal/mol
Surface area9720 Å2
MethodPISA
Unit cell
Length a, b, c (Å)45.188, 45.188, 331.301
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number179
Space group name H-MP6522
Space group name HallP652(x,y,z+1/12)
Symmetry operation#1: x,y,z
#2: x-y,x,z+5/6
#3: y,-x+y,z+1/6
#4: -y,x-y,z+2/3
#5: -x+y,-x,z+1/3
#6: x-y,-y,-z
#7: -x,-x+y,-z+1/3
#8: -x,-y,z+1/2
#9: y,x,-z+2/3
#10: -y,-x,-z+1/6
#11: -x+y,y,-z+1/2
#12: x,x-y,-z+5/6
Components on special symmetry positions
IDModelComponents
11A-622-

HOH

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Components

#1: Protein Cellular tumor antigen p53


Mass: 24530.812 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
#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 146 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 1.99 Å3/Da / Density % sol: 38.2 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: Protein solution: 5.5-6.0 mg/ml in 25 mM HEPES (pH 7.5), 300 mM NaCl, 0.5 mM TCEP. Reservoir buffer: 0.7 M sodium citrate and 0.1 M bis-tris-propane (pH 7.0).

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 0.9999 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jul 5, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9999 Å / Relative weight: 1
ReflectionResolution: 1.69→39.1 Å / Num. obs: 24105 / % possible obs: 99.9 % / Redundancy: 7.2 % / Biso Wilson estimate: 26.1660365092 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.053 / Net I/σ(I): 17.6
Reflection shellResolution: 1.69→1.72 Å / Redundancy: 7.7 % / Rmerge(I) obs: 0.932 / Mean I/σ(I) obs: 2.4 / Num. unique obs: 1190 / CC1/2: 0.803 / % possible all: 99.9

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Processing

Software
NameVersionClassification
PHENIX1.10.1_2155refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.69→39.1 Å / SU ML: 0.16834663906 / Cross valid method: FREE R-VALUE / σ(F): 1.33789898475 / Phase error: 21.056901831
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.218076194934 1249 5.21263720212 %
Rwork0.195810433002 22712 -
obs0.196997491503 23961 99.7626779915 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 31.0121303363 Å2
Refinement stepCycle: LAST / Resolution: 1.69→39.1 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1453 0 5 146 1604
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.006459401028121521
X-RAY DIFFRACTIONf_angle_d0.7986232856842067
X-RAY DIFFRACTIONf_chiral_restr0.0557661251484226
X-RAY DIFFRACTIONf_plane_restr0.00559003417458275
X-RAY DIFFRACTIONf_dihedral_angle_d17.8101002012933
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.69-1.75770.2945240830921280.2536207285072449X-RAY DIFFRACTION99.8063516654
1.7577-1.83770.2348322098881410.2308037507882417X-RAY DIFFRACTION99.7270955166
1.8377-1.93460.2680589230111500.2002641497332452X-RAY DIFFRACTION99.9231950845
1.9346-2.05580.2241149785951360.1994470295682490X-RAY DIFFRACTION99.9238964992
2.0558-2.21450.2212955290531290.1953818473022451X-RAY DIFFRACTION99.7294163123
2.2145-2.43730.2245644318681360.2017180800352508X-RAY DIFFRACTION99.9621928166
2.4373-2.78990.26050785621320.2097647353432551X-RAY DIFFRACTION99.9627421759
2.7899-3.51470.1930170802431440.1972263194492593X-RAY DIFFRACTION99.8540678584
3.5147-39.10.205780403741530.1810952333542801X-RAY DIFFRACTION99.0942636699

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