[English] 日本語
Yorodumi
- PDB-8dc6: Crystal structure of p53 Y220C covalently bound to indole KG6 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8dc6
TitleCrystal structure of p53 Y220C covalently bound to indole KG6
ComponentsCellular tumor antigen p53
KeywordsCELL CYCLE / p53 / TP53 / tumor suppressor
Function / homology
Function and homology information


negative regulation of helicase 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 / negative regulation of pentose-phosphate shunt / ATP-dependent DNA/DNA annealing activity ...negative regulation of helicase 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 / negative regulation of pentose-phosphate shunt / ATP-dependent DNA/DNA annealing activity / Activation of NOXA and translocation to mitochondria / regulation of cell cycle G2/M phase transition / oligodendrocyte apoptotic process / negative regulation of miRNA processing / intrinsic apoptotic signaling pathway in response to hypoxia / regulation of fibroblast apoptotic process / positive regulation of thymocyte apoptotic process / oxidative stress-induced premature senescence / regulation of tissue remodeling / positive regulation of mitochondrial membrane permeability / mRNA transcription / bone marrow development / positive regulation of programmed necrotic cell death / circadian behavior / T cell proliferation involved in immune response / regulation of mitochondrial membrane permeability involved in apoptotic process / germ cell nucleus / RUNX3 regulates CDKN1A transcription / glucose catabolic process to lactate via pyruvate / TP53 Regulates Transcription of Death Receptors and Ligands / Activation of PUMA and translocation to mitochondria / TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain / regulation of DNA damage response, signal transduction by p53 class mediator / histone deacetylase regulator activity / negative regulation of glial cell proliferation / Regulation of TP53 Activity through Association with Co-factors / negative regulation of neuroblast proliferation / mitochondrial DNA repair / T cell lineage commitment / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / ER overload response / thymocyte apoptotic process / B cell lineage commitment / TP53 Regulates Transcription of Caspase Activators and Caspases / cardiac septum morphogenesis / negative regulation of mitophagy / negative regulation of DNA replication / entrainment of circadian clock by photoperiod / negative regulation of telomere maintenance via telomerase / Zygotic genome activation (ZGA) / positive regulation of release of cytochrome c from mitochondria / PI5P Regulates TP53 Acetylation / Association of TriC/CCT with target proteins during biosynthesis / necroptotic process / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / TFIID-class transcription factor complex binding / SUMOylation of transcription factors / TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain / intrinsic apoptotic signaling pathway by p53 class mediator / rRNA transcription / negative regulation of reactive oxygen species metabolic process / Transcriptional Regulation by VENTX / cellular response to UV-C / replicative senescence / general transcription initiation factor binding / cellular response to actinomycin D / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / positive regulation of RNA polymerase II transcription preinitiation complex assembly / neuroblast proliferation / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of execution phase of apoptosis / viral process / Pyroptosis / hematopoietic stem cell differentiation / response to X-ray / embryonic organ development / chromosome organization / type II interferon-mediated signaling pathway / somitogenesis / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / hematopoietic progenitor cell differentiation / glial cell proliferation / negative regulation of fibroblast proliferation / positive regulation of cardiac muscle cell apoptotic process / core promoter sequence-specific DNA binding / negative regulation of stem cell proliferation / cellular response to glucose starvation / mitophagy / cis-regulatory region sequence-specific DNA binding / positive regulation of intrinsic apoptotic signaling pathway / Regulation of TP53 Activity through Acetylation / gastrulation / response to salt stress / 14-3-3 protein binding / mitotic G1 DNA damage checkpoint signaling / negative regulation of proteolysis / MDM2/MDM4 family protein binding / cardiac muscle cell apoptotic process / transcription repressor complex / intrinsic apoptotic signaling pathway
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
Chem-R4F / Cellular tumor antigen p53
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.60000908706 Å
AuthorsGuiley, K.Z. / Shokat, K.M.
Funding support United States, 1items
OrganizationGrant numberCountry
Howard Hughes Medical Institute (HHMI)DRG: 2399-20 United States
CitationJournal: Cancer Discov / Year: 2023
Title: A Small Molecule Reacts with the p53 Somatic Mutant Y220C to Rescue Wild-type Thermal Stability.
Authors: Guiley, K.Z. / Shokat, K.M.
History
DepositionJun 15, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 12, 2022Provider: repository / Type: Initial release
Revision 1.1Jan 18, 2023Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation.year
Revision 1.2Oct 25, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.3Oct 23, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Cellular tumor antigen p53
B: Cellular tumor antigen p53
C: Cellular tumor antigen p53
D: Cellular tumor antigen p53
hetero molecules


Theoretical massNumber of molelcules
Total (without water)101,92427
Polymers99,5044
Non-polymers2,42023
Water11,205622
1
A: Cellular tumor antigen p53
hetero molecules


Theoretical massNumber of molelcules
Total (without water)25,6378
Polymers24,8761
Non-polymers7617
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Cellular tumor antigen p53
hetero molecules


Theoretical massNumber of molelcules
Total (without water)25,4697
Polymers24,8761
Non-polymers5936
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
C: Cellular tumor antigen p53
hetero molecules


Theoretical massNumber of molelcules
Total (without water)25,3736
Polymers24,8761
Non-polymers4975
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
4
D: Cellular tumor antigen p53
hetero molecules


Theoretical massNumber of molelcules
Total (without water)25,4456
Polymers24,8761
Non-polymers5695
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)91.040, 105.750, 105.750
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2

-
Components

-
Protein , 1 types, 4 molecules ABCD

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


Mass: 24876.016 Da / Num. of mol.: 4 / Mutation: Y220C
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

-
Non-polymers , 5 types, 645 molecules

#2: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Zn / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 13 / Source method: obtained synthetically / Formula: SO4
#4: Chemical
ChemComp-R4F / 1-(2-methylprop-2-enoyl)-1H-indole-3-carbaldehyde, bound form


Mass: 215.248 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C13H13NO2 / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 622 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.56 Å3/Da / Density % sol: 51.91 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7 / Details: 100 mM HEPES, 2.2M MgSO4

-
Data collection

DiffractionMean temperature: 80 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 8.2.1 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Dec 16, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.6→57.78 Å / Num. obs: 133925 / % possible obs: 99 % / Redundancy: 2 % / Biso Wilson estimate: 15.2051228967 Å2 / CC1/2: 0.999 / Net I/σ(I): 20.3
Reflection shellResolution: 1.6→1.6 Å / Num. unique obs: 13159 / CC1/2: 0.947

-
Processing

Software
NameVersionClassification
Blu-Icedata collection
iMOSFLMdata reduction
Aimlessdata scaling
PHASERphasing
PHENIX1.20.1refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2J1X

2j1x


Resolution: 1.60000908706→47.2928377241 Å / SU ML: 0.166831907581 / Cross valid method: FREE R-VALUE / σ(F): 1.34297848669 / Phase error: 18.9413581216
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.202329214824 6607 4.9344635722 %
Rwork0.181395773567 127288 -
obs0.182425826238 133895 99.3721287507 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 21.5712440779 Å2
Refinement stepCycle: LAST / Resolution: 1.60000908706→47.2928377241 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6053 0 135 622 6810
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.008128426738046401
X-RAY DIFFRACTIONf_angle_d1.263361124168727
X-RAY DIFFRACTIONf_chiral_restr0.0631557693318938
X-RAY DIFFRACTIONf_plane_restr0.008359594299151135
X-RAY DIFFRACTIONf_dihedral_angle_d15.20336727513893
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.60000908706-1.61820.2593434833872030.2294096579964140X-RAY DIFFRACTION98.4583994559
1.6182-1.63720.2396939964881970.2219332331334172X-RAY DIFFRACTION98.6230248307
1.6372-1.65720.2310893119322360.2046669169844211X-RAY DIFFRACTION98.5812458435
1.6572-1.67820.2116046051681810.194568896884156X-RAY DIFFRACTION98.5457850489
1.6782-1.70030.2360738199232270.1929832624284217X-RAY DIFFRACTION98.9755011136
1.7003-1.72360.2305804207082370.1922238463094140X-RAY DIFFRACTION98.9376130199
1.7236-1.74820.208073631942310.192657457494140X-RAY DIFFRACTION99.0707162285
1.7482-1.77430.2152791601242460.1883718855734165X-RAY DIFFRACTION98.9457155675
1.7743-1.8020.1936798361442150.1766686712574185X-RAY DIFFRACTION98.9431077131
1.802-1.83150.1897525996362000.1727455536414252X-RAY DIFFRACTION98.9993328886
1.8315-1.86310.2028088291312320.1751949665974202X-RAY DIFFRACTION99.1502683363
1.8631-1.8970.1910395782862460.1802761449884153X-RAY DIFFRACTION99.2106450158
1.897-1.93350.2250785455732000.1908662411934213X-RAY DIFFRACTION99.3471409275
1.9335-1.9730.2102461191242630.186694732554173X-RAY DIFFRACTION99.4173016584
1.973-2.01590.2118490355462120.1729832201594215X-RAY DIFFRACTION99.4607953269
2.0159-2.06280.2066340575982150.1831909251484265X-RAY DIFFRACTION99.6662958843
2.0628-2.11430.1905399277822000.1837640422274265X-RAY DIFFRACTION99.3104982206
2.1143-2.17150.2127762517072330.1789277408384205X-RAY DIFFRACTION99.6631484393
2.1715-2.23540.2092736935112080.1779591091494243X-RAY DIFFRACTION99.7311225633
2.2354-2.30760.1848225343092360.1753876081224238X-RAY DIFFRACTION99.5771199644
2.3076-2.390.2018160487231940.1868809563254302X-RAY DIFFRACTION99.9111111111
2.39-2.48570.199929566161910.1842849568254293X-RAY DIFFRACTION99.7774810859
2.4857-2.59880.2233420196922480.1868760216384238X-RAY DIFFRACTION99.8664292075
2.5988-2.73580.2063689303062330.1927999745224285X-RAY DIFFRACTION99.8894539023
2.7358-2.90720.2235025532031990.1941619058134305X-RAY DIFFRACTION99.9556147359
2.9072-3.13160.227211481572180.1885397556434296X-RAY DIFFRACTION99.9778516058
3.1316-3.44670.1899848026242390.1687232544284301X-RAY DIFFRACTION100
3.4467-3.94520.1919829459972120.1583797318214383X-RAY DIFFRACTION99.9782419495
3.9452-4.96970.1663735917112220.1597034193344397X-RAY DIFFRACTION99.9783549784

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more