[English] 日本語
Yorodumi
- PDB-5g4m: Crystal structure of the p53 cancer mutant Y220C in complex with ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5g4m
TitleCrystal structure of the p53 cancer mutant Y220C in complex with a monofluorinated derivative of the small molecule stabilizer Phikan083
ComponentsCELLULAR TUMOR ANTIGEN P53
KeywordsTRANSCRIPTION / P53 / CANCER / TUMOR SUPPRESSION / DNA BINDING / CANCER THERAPY / SMALL-MOLECULE STABILIZERS / MOLECULAR CHAPERONE / FLUORINE-PROTEIN INTERACTIONS
Function / homology
Function and homology information


negative regulation of helicase activity / signal transduction by p53 class mediator / Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / regulation of cell cycle G2/M phase transition / negative regulation of G1 to G0 transition / Transcriptional activation of cell cycle inhibitor p21 / negative regulation of pentose-phosphate shunt / Activation of NOXA and translocation to mitochondria / ATP-dependent DNA/DNA annealing activity ...negative regulation of helicase activity / signal transduction by p53 class mediator / Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / regulation of cell cycle G2/M phase transition / negative regulation of G1 to G0 transition / Transcriptional activation of cell cycle inhibitor p21 / negative regulation of pentose-phosphate shunt / Activation of NOXA and translocation to mitochondria / ATP-dependent DNA/DNA annealing activity / oligodendrocyte apoptotic process / positive regulation of thymocyte apoptotic process / oxidative stress-induced premature senescence / bone marrow development / cellular response to actinomycin D / circadian behavior / positive regulation of programmed necrotic cell death / RUNX3 regulates CDKN1A transcription / 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 / mRNA transcription / Regulation of TP53 Activity through Association with Co-factors / Urea cycle / ER overload response / hematopoietic stem cell differentiation / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / TP53 Regulates Transcription of Caspase Activators and Caspases / intrinsic apoptotic signaling pathway by p53 class mediator / entrainment of circadian clock by photoperiod / Zygotic genome activation (ZGA) / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / PI5P Regulates TP53 Acetylation / positive regulation of release of cytochrome c from mitochondria / Association of TriC/CCT with target proteins during biosynthesis / hematopoietic progenitor cell differentiation / negative regulation of telomere maintenance via telomerase / 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 in response to DNA damage by p53 class mediator / replicative senescence / Transcriptional Regulation by VENTX / TFIID-class transcription factor complex binding / viral process / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / determination of adult lifespan / Pyroptosis / positive regulation of RNA polymerase II transcription preinitiation complex assembly / general transcription initiation factor binding / negative regulation of fibroblast proliferation / positive regulation of execution phase of apoptosis / type II interferon-mediated signaling pathway / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / cellular response to glucose starvation / core promoter sequence-specific DNA binding / cis-regulatory region sequence-specific DNA binding / Regulation of TP53 Activity through Acetylation / intrinsic apoptotic signaling pathway / mitotic G1 DNA damage checkpoint signaling / positive regulation of intrinsic apoptotic signaling pathway / 14-3-3 protein binding / response to gamma radiation / MDM2/MDM4 family protein binding / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / protein phosphatase 2A binding / DNA damage response, signal transduction by p53 class mediator / transcription initiation-coupled chromatin remodeling / molecular function activator activity / Regulation of PTEN gene transcription / tumor necrosis factor-mediated signaling pathway / cellular response to ionizing radiation / cellular response to xenobiotic stimulus / TP53 Regulates Metabolic Genes / TP53 Regulates Transcription of DNA Repair Genes / cellular response to gamma radiation / Regulation of NF-kappa B signaling / mRNA 3'-UTR binding / protein tetramerization / molecular condensate scaffold activity / promoter-specific chromatin binding / Stabilization of p53 / negative regulation of cell growth / nucleotide-excision repair / G2/M Checkpoints / receptor tyrosine kinase binding / Autodegradation of the E3 ubiquitin ligase COP1 / PML body / cellular senescence / PKR-mediated signaling / positive regulation of miRNA transcription / Oncogene Induced Senescence / DNA-binding transcription repressor activity, RNA polymerase II-specific / Regulation of TP53 Activity through Methylation / G2/M DNA damage checkpoint / DNA Damage/Telomere Stress Induced Senescence / Pre-NOTCH Transcription and Translation / intracellular protein localization / transcription coactivator binding / positive regulation of reactive oxygen species metabolic process / histone deacetylase binding
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 ...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
Chem-O82 / Cellular tumor antigen p53
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.38 Å
AuthorsJoerger, A.C. / Bauer, M.
CitationJournal: Acs Chem.Biol. / Year: 2016
Title: Harnessing Fluorine-Sulfur Contacts and Multipolar Interactions for the Design of P53 Mutant Y220C Rescue Drugs.
Authors: Bauer, M.R. / Jones, R.N. / Baud, M.G.J. / Wilcken, R. / Boeckler, F.M. / Fersht, A.R. / Joerger, A.C. / Spencer, J.
History
DepositionMay 13, 2016Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jun 22, 2016Provider: repository / Type: Initial release
Revision 1.1Sep 28, 2016Group: Database references
Revision 1.2May 8, 2019Group: Data collection / Experimental preparation / Other
Category: exptl_crystal_grow / pdbx_database_proc / pdbx_database_status
Item: _exptl_crystal_grow.temp / _pdbx_database_status.recvd_author_approval
Revision 1.3May 15, 2019Group: Data collection / Experimental preparation / Category: exptl_crystal_grow / Item: _exptl_crystal_grow.method
Revision 1.4Jan 10, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: CELLULAR TUMOR ANTIGEN P53
B: CELLULAR TUMOR ANTIGEN P53
hetero molecules


Theoretical massNumber of molelcules
Total (without water)49,8598
Polymers49,0622
Non-polymers7986
Water8,287460
1
A: CELLULAR TUMOR ANTIGEN P53
hetero molecules


Theoretical massNumber of molelcules
Total (without water)24,8533
Polymers24,5311
Non-polymers3222
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: CELLULAR TUMOR ANTIGEN P53
hetero molecules


Theoretical massNumber of molelcules
Total (without water)25,0075
Polymers24,5311
Non-polymers4764
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)65.030, 71.144, 105.144
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 1 types, 2 molecules AB

#1: Protein CELLULAR TUMOR ANTIGEN P53 / P53 / ANTIGEN NY-CO-13 / PHOSPHOPROTEIN P53 / TUMOR SUPPRESSOR P53


Mass: 24530.811 Da / Num. of mol.: 2 / Fragment: DNA-BINDING DOMAIN, UNP RESIDUES 94-312 / Mutation: YES
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli) / References: UniProt: P04637

-
Non-polymers , 5 types, 466 molecules

#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-O82 / 1-[9-(2-fluoroethyl)-9H-carbazol-3-yl]-N-methylmethanamine


Mass: 256.318 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C16H17FN2
#4: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#5: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


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


Mass: 18.015 Da / Num. of mol.: 460 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION

-
Sample preparation

CrystalDensity Matthews: 2.5 Å3/Da / Density % sol: 51 % / Description: NONE
Crystal growTemperature: 294 K / Method: vapor diffusion, sitting drop
Details: SITTING-DROP VAPOR DIFFUSION AT 21 DEGREE C. 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) ...Details: SITTING-DROP VAPOR DIFFUSION AT 21 DEGREE C. 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. SOAKING BUFFER: SATURATED SOLUTION OF COMPOUND IN 100 MM HEPES, PH 7.2, 10 MM SODIUM PHOSPHATE, PH 7.2, 19% (W/V) POLYETHYLENE GLYCOL 4000, 20 % (V/V) GLYCEROL, 150 MM KCL.

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.9795
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 1.38→29.6 Å / Num. obs: 99536 / % possible obs: 98.9 % / Observed criterion σ(I): 2 / Redundancy: 4.8 % / Rmerge(I) obs: 0.04 / Net I/σ(I): 19.2
Reflection shellResolution: 1.38→1.45 Å / Redundancy: 4.8 % / Rmerge(I) obs: 0.51 / Mean I/σ(I) obs: 3.4 / % possible all: 98.6

-
Processing

Software
NameVersionClassification
PHENIX(DEV_2386: ???)refinement
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 2J1X

2j1x


Resolution: 1.38→29.573 Å / SU ML: 0.1 / σ(F): 1.35 / Phase error: 16.29 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.1696 4997 5 %
Rwork0.1458 --
obs0.1469 99417 98.66 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.38→29.573 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3072 0 50 460 3582
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0053327
X-RAY DIFFRACTIONf_angle_d0.784538
X-RAY DIFFRACTIONf_dihedral_angle_d18.7221285
X-RAY DIFFRACTIONf_chiral_restr0.083492
X-RAY DIFFRACTIONf_plane_restr0.006597
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.38-1.39570.23221770.20283064X-RAY DIFFRACTION97
1.3957-1.41210.24181640.18893121X-RAY DIFFRACTION99
1.4121-1.42930.20321490.18263101X-RAY DIFFRACTION98
1.4293-1.44740.21821870.17313095X-RAY DIFFRACTION99
1.4474-1.46650.22061740.16723080X-RAY DIFFRACTION99
1.4665-1.48660.19831790.1613110X-RAY DIFFRACTION98
1.4866-1.50780.20031530.15093148X-RAY DIFFRACTION99
1.5078-1.53030.1821550.14313117X-RAY DIFFRACTION99
1.5303-1.55420.17641470.13913110X-RAY DIFFRACTION98
1.5542-1.57970.15921680.13193133X-RAY DIFFRACTION99
1.5797-1.60690.15871610.12983127X-RAY DIFFRACTION99
1.6069-1.63610.14971620.12323102X-RAY DIFFRACTION99
1.6361-1.66760.15191680.11733165X-RAY DIFFRACTION99
1.6676-1.70160.14391770.1143097X-RAY DIFFRACTION99
1.7016-1.73860.13191710.11673124X-RAY DIFFRACTION99
1.7386-1.77910.14311710.11753109X-RAY DIFFRACTION98
1.7791-1.82360.14891830.12123118X-RAY DIFFRACTION99
1.8236-1.87290.17931810.13083109X-RAY DIFFRACTION98
1.8729-1.9280.15721740.12863165X-RAY DIFFRACTION99
1.928-1.99020.15621550.1313131X-RAY DIFFRACTION99
1.9902-2.06130.16141580.13313194X-RAY DIFFRACTION99
2.0613-2.14380.1651890.13883170X-RAY DIFFRACTION99
2.1438-2.24130.17771660.14013174X-RAY DIFFRACTION99
2.2413-2.35950.18431580.14713155X-RAY DIFFRACTION99
2.3595-2.50720.17681610.14923156X-RAY DIFFRACTION98
2.5072-2.70070.14941690.15473213X-RAY DIFFRACTION99
2.7007-2.97220.18431700.163206X-RAY DIFFRACTION99
2.9722-3.40180.1991520.15413217X-RAY DIFFRACTION98
3.4018-4.28380.15091680.14113215X-RAY DIFFRACTION98
4.2838-29.57960.16831500.16463394X-RAY DIFFRACTION98

+
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