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- PDB-4mzi: Crystal structure of a human mutant p53 -

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Basic information

Entry
Database: PDB / ID: 4mzi
TitleCrystal structure of a human mutant p53
ComponentsCellular tumor antigen p53P53
KeywordsANTITUMOR PROTEIN / loop L1 / tumor suppressor / antitumour protein / dna binding
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 / T cell proliferation involved in immune response / regulation of mitochondrial membrane permeability involved in apoptotic process / histone deacetylase regulator activity / RUNX3 regulates CDKN1A transcription / germ cell nucleus / 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 neuroblast proliferation / negative regulation of glial cell proliferation / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / Regulation of TP53 Activity through Association with Co-factors / positive regulation of execution phase of apoptosis / mitochondrial DNA repair / T cell lineage commitment / negative regulation of DNA replication / ER overload response / B cell lineage commitment / thymocyte apoptotic process / positive regulation of cardiac muscle cell 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 / 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 / rRNA transcription / 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 / mitophagy / negative regulation of telomere maintenance via telomerase / SUMOylation of transcription factors / intrinsic apoptotic signaling pathway by p53 class mediator / general transcription initiation factor binding / neuroblast proliferation / cellular response to actinomycin D / Transcriptional Regulation by VENTX / response to X-ray / DNA damage response, signal transduction by p53 class mediator / replicative senescence / chromosome organization / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / gastrulation / cellular response to UV-C / response to inorganic substance / hematopoietic stem cell differentiation / positive regulation of RNA polymerase II transcription preinitiation complex assembly / negative regulation of reactive oxygen species metabolic process / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / MDM2/MDM4 family protein binding / embryonic organ development / glial cell proliferation / 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 / somitogenesis / type II interferon-mediated signaling pathway / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / positive regulation of intrinsic apoptotic signaling pathway / negative regulation of stem cell proliferation / core promoter sequence-specific DNA binding / negative regulation of fibroblast proliferation / response to salt stress / cardiac muscle cell apoptotic process / transcription initiation-coupled chromatin remodeling / mitotic G1 DNA damage checkpoint signaling / Regulation of TP53 Activity through Acetylation
Similarity search - Function
Immunoglobulin-like - #720 / 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 ...Immunoglobulin-like - #720 / 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 / Immunoglobulin-like / Sandwich / Mainly Beta
Similarity search - Domain/homology
Cellular tumor antigen p53
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.25 Å
AuthorsEmamzadah, S. / Tropia, L. / Vincenti, I. / Falquet, B. / Halazonetis, T.D.
CitationJournal: J.Mol.Biol. / Year: 2014
Title: Reversal of the DNA-Binding-Induced Loop L1 Conformational Switch in an Engineered Human p53 Protein.
Authors: Emamzadah, S. / Tropia, L. / Vincenti, I. / Falquet, B. / Halazonetis, T.D.
History
DepositionSep 30, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 15, 2014Provider: repository / Type: Initial release
Revision 1.1Feb 12, 2014Group: Database references
Revision 1.2Dec 21, 2022Group: Database references / Derived calculations / Category: database_2 / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.3May 22, 2024Group: Data collection / Category: chem_comp_atom / chem_comp_bond

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Cellular tumor antigen p53
hetero molecules


Theoretical massNumber of molelcules
Total (without water)22,5952
Polymers22,5301
Non-polymers651
Water3,855214
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)44.707, 62.428, 73.701
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

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Components

#1: Protein Cellular tumor antigen p53 / P53 / Antigen NY-CO-13 / Phosphoprotein p53 / Tumor suppressor p53


Mass: 22529.635 Da / Num. of mol.: 1 / Fragment: UNP residues 94-292 / Mutation: S121F, V122G
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
#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 214 / Source method: isolated from a natural source / Formula: H2O

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION

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Sample preparation

CrystalDensity Matthews: 2.28 Å3/Da / Density % sol: 46.11 %
Crystal growTemperature: 278 K / Method: vapor diffusion, hanging drop / pH: 6.8
Details: pH 6.8, VAPOR DIFFUSION, HANGING DROP, temperature 278K

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Data collection

DiffractionMean temperature: 85 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID29 / Wavelength: 0.9334 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Apr 29, 2013
RadiationMonochromator: Pt coated Si mirror / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9334 Å / Relative weight: 1
ReflectionResolution: 1.25→30 Å / Num. obs: 8315 / % possible obs: 98.9 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0

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Processing

Software
NameClassification
MxCuBEdata collection
CNSrefinement
MOSFLMdata reduction
SCALAdata scaling
CNSphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.25→30 Å / σ(F): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflectionSelection details
Rfree0.201 57048 random
Rwork0.198 --
obs0.198 8315 -
Refinement stepCycle: LAST / Resolution: 1.25→30 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1518 0 1 214 1733
Refine LS restraintsType: rmsd bonds / Dev ideal: 0.004

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