[English] 日本語
Yorodumi
- PDB-4hfz: Crystal Structure of an MDM2/P53 Peptide Complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4hfz
TitleCrystal Structure of an MDM2/P53 Peptide Complex
Components
  • Cellular tumor antigen p53
  • E3 ubiquitin-protein ligase Mdm2
KeywordsLIGASE / MDM2 / p53 / Surface Entropy Reduction / Mutant Validation
Function / homology
Function and homology information


cellular response to vitamin B1 / response to formaldehyde / response to water-immersion restraint stress / response to ether / traversing start control point of mitotic cell cycle / atrial septum development / fibroblast activation / regulation of protein catabolic process at postsynapse, modulating synaptic transmission / Trafficking of AMPA receptors / receptor serine/threonine kinase binding ...cellular response to vitamin B1 / response to formaldehyde / response to water-immersion restraint stress / response to ether / traversing start control point of mitotic cell cycle / atrial septum development / fibroblast activation / regulation of protein catabolic process at postsynapse, modulating synaptic transmission / Trafficking of AMPA receptors / receptor serine/threonine kinase binding / peroxisome proliferator activated receptor binding / negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator / 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 / positive regulation of vascular associated smooth muscle cell migration / 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 / positive regulation of thymocyte apoptotic process / oxidative stress-induced premature senescence / regulation of tissue remodeling / negative regulation of protein processing / positive regulation of mitochondrial membrane permeability / regulation of fibroblast apoptotic process / SUMO transferase activity / response to steroid hormone / mRNA transcription / bone marrow development / circadian behavior / T cell proliferation involved in immune response / positive regulation of programmed necrotic cell death / regulation of mitochondrial membrane permeability involved in apoptotic process / histone deacetylase regulator activity / atrioventricular valve morphogenesis / AKT phosphorylates targets in the cytosol / response to iron ion / germ cell nucleus / RUNX3 regulates CDKN1A transcription / : / NEDD8 ligase activity / TP53 Regulates Transcription of Death Receptors and Ligands / TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain / Activation of PUMA and translocation to mitochondria / cellular response to peptide hormone stimulus / endocardial cushion morphogenesis / Regulation of TP53 Activity through Association with Co-factors / regulation of DNA damage response, signal transduction by p53 class mediator / negative regulation of glial cell proliferation / negative regulation of neuroblast proliferation / ventricular septum development / T cell lineage commitment / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / mitochondrial DNA repair / positive regulation of muscle cell differentiation / thymocyte apoptotic process / ER overload response / TP53 Regulates Transcription of Caspase Activators and Caspases / cardiac septum morphogenesis / B cell lineage commitment / entrainment of circadian clock by photoperiod / regulation of postsynaptic neurotransmitter receptor internalization / SUMOylation of ubiquitinylation proteins / cellular response to alkaloid / negative regulation of mitophagy / blood vessel development / Constitutive Signaling by AKT1 E17K in Cancer / ligase activity / negative regulation of DNA replication / Zygotic genome activation (ZGA) / cellular response to antibiotic / Association of TriC/CCT with target proteins during biosynthesis / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / PI5P Regulates TP53 Acetylation / negative regulation of DNA damage response, signal transduction by p53 class mediator / regulation of protein catabolic process / necroptotic process / negative regulation of signal transduction by p53 class mediator / negative regulation of telomere maintenance via telomerase / positive regulation of release of cytochrome c from mitochondria / SUMOylation of transcription factors / TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain / TFIID-class transcription factor complex binding / cellular response to actinomycin D / intrinsic apoptotic signaling pathway by p53 class mediator / negative regulation of reactive oxygen species metabolic process / rRNA transcription / Transcriptional Regulation by VENTX / cellular response to UV-C / viral process / response to magnesium ion
Similarity search - Function
E3 ubiquitin-protein ligase Mdm2 / MDM2, modified RING finger, HC subclass / MDM2 / SWIB/MDM2 domain / p53 negative regulator Mdm2/Mdm4 / SWIB/MDM2 domain / SWIB/MDM2 domain / SWIB/MDM2 domain profile. / SWIB/MDM2 domain superfamily / Cellular tumor antigen p53, transactivation domain 2 ...E3 ubiquitin-protein ligase Mdm2 / MDM2, modified RING finger, HC subclass / MDM2 / SWIB/MDM2 domain / p53 negative regulator Mdm2/Mdm4 / SWIB/MDM2 domain / SWIB/MDM2 domain / SWIB/MDM2 domain profile. / SWIB/MDM2 domain superfamily / Cellular tumor antigen p53, transactivation domain 2 / Transactivation domain 2 / p53 transactivation domain / P53 transactivation motif / Zn-finger in Ran binding protein and others / : / 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 / Zinc finger, C3HC4 type (RING finger) / Zinc finger RanBP2 type profile. / Zinc finger, RanBP2-type superfamily / Zinc finger RanBP2-type signature. / Zinc finger, RanBP2-type / p53-like transcription factor, DNA-binding / Zinc finger RING-type profile. / Zinc finger, RING-type / Zinc finger, RING/FYVE/PHD-type / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Cellular tumor antigen p53 / E3 ubiquitin-protein ligase Mdm2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.694 Å
AuthorsAnil, B. / Riedinger, C. / Endicott, J.A. / Noble, M.E.M.
CitationJournal: Acta Crystallogr.,Sect.D / Year: 2013
Title: The structure of an MDM2-Nutlin-3a complex solved by the use of a validated MDM2 surface-entropy reduction mutant.
Authors: Anil, B. / Riedinger, C. / Endicott, J.A. / Noble, M.E.
History
DepositionOct 5, 2012Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 31, 2013Provider: repository / Type: Initial release
Revision 1.1Aug 21, 2013Group: Database references
Revision 1.2Feb 28, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_ncs_dom_lim / 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_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id / _struct_ref_seq_dif.details / _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: E3 ubiquitin-protein ligase Mdm2
B: Cellular tumor antigen p53
C: E3 ubiquitin-protein ligase Mdm2
D: Cellular tumor antigen p53
hetero molecules


Theoretical massNumber of molelcules
Total (without water)28,5505
Polymers28,4544
Non-polymers961
Water86548
1
A: E3 ubiquitin-protein ligase Mdm2
B: Cellular tumor antigen p53
hetero molecules


Theoretical massNumber of molelcules
Total (without water)14,3233
Polymers14,2272
Non-polymers961
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1300 Å2
ΔGint-23 kcal/mol
Surface area5620 Å2
MethodPISA
2
C: E3 ubiquitin-protein ligase Mdm2
D: Cellular tumor antigen p53


Theoretical massNumber of molelcules
Total (without water)14,2272
Polymers14,2272
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1100 Å2
ΔGint-10 kcal/mol
Surface area6540 Å2
MethodPISA
Unit cell
Length a, b, c (Å)52.944, 52.944, 196.201
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number96
Space group name H-MP43212
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21C

NCS domain segments:

Component-ID: _ / Ens-ID: 1 / Beg auth comp-ID: THR / Beg label comp-ID: THR / End auth comp-ID: LEU / End label comp-ID: LEU / Refine code: _ / Auth seq-ID: 26 - 107 / Label seq-ID: 10 - 91

Dom-IDAuth asym-IDLabel asym-ID
1AA
2CC

-
Components

#1: Protein E3 ubiquitin-protein ligase Mdm2 / Double minute 2 protein / Hdm2 / Oncoprotein Mdm2 / p53-binding protein Mdm2


Mass: 12419.212 Da / Num. of mol.: 2 / Fragment: p53 binding domain (residues 17-125) / Mutation: E69A, K70A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MDM2 / Plasmid: pGEX6P1 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 (DE23)
References: UniProt: Q00987, Ligases; Forming carbon-nitrogen bonds; Acid-amino-acid ligases (peptide synthases)
#2: Protein/peptide Cellular tumor antigen p53 / Antigen NY-CO-13 / Phosphoprotein p53 / Tumor suppressor p53


Mass: 1807.973 Da / Num. of mol.: 2 / Fragment: residues 15-29 / Source method: obtained synthetically / Details: Synthetic construct / Source: (synth.) Homo sapiens (human) / References: UniProt: P04637
#3: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 48 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.42 Å3/Da / Density % sol: 49.09 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.4
Details: 0.2 M (NH4)2SO4, pH 4.6 and 30% w/v PEG 8000, VAPOR DIFFUSION, SITTING DROP, temperature 277K

-
Data collection

DiffractionMean temperature: 296 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID29 / Wavelength: 0.96 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Feb 28, 2011
RadiationMonochromator: Si 111 channel / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.96 Å / Relative weight: 1
ReflectionResolution: 2.694→46.68 Å / Num. obs: 8223 / % possible obs: 96.6 % / Observed criterion σ(F): 3 / Observed criterion σ(I): 5
Reflection shellResolution: 2.694→2.85 Å / % possible all: 99.8

-
Processing

Software
NameVersionClassification
XDSdata scaling
PHASERphasing
REFMAC5.6.0117refinement
XDSdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.694→41.12 Å / Cor.coef. Fo:Fc: 0.93 / Cor.coef. Fo:Fc free: 0.896 / SU B: 19.73 / SU ML: 0.212 / Cross valid method: THROUGHOUT / σ(F): 10 / ESU R: 0.792 / ESU R Free: 0.323 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT
RfactorNum. reflection% reflectionSelection details
Rfree0.24679 376 4.6 %RANDOM
Rwork0.19527 ---
obs0.19777 7733 96.86 %-
all-8367 --
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 38.15 Å2
Baniso -1Baniso -2Baniso -3
1-1.43 Å20 Å20 Å2
2--1.43 Å20 Å2
3----2.85 Å2
Refinement stepCycle: LAST / Resolution: 2.694→41.12 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1620 0 5 48 1673
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0140.021669
X-RAY DIFFRACTIONr_angle_refined_deg1.6341.9972254
X-RAY DIFFRACTIONr_dihedral_angle_1_deg4.3045194
X-RAY DIFFRACTIONr_dihedral_angle_2_deg43.8723.62369
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.85915316
X-RAY DIFFRACTIONr_dihedral_angle_4_deg22.314158
X-RAY DIFFRACTIONr_chiral_restr0.1130.2258
X-RAY DIFFRACTIONr_gen_planes_refined0.0090.0211200
Refine LS restraints NCS

Ens-ID: 1 / Number: 93 / Refine-ID: X-RAY DIFFRACTION / Type: interatomic distance / Rms dev position: 0.09 Å / Weight position: 0.05

Dom-IDAuth asym-ID
1A
2C
LS refinement shellResolution: 2.694→2.764 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.385 22 -
Rwork0.238 456 -
obs--93.73 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
13.7099-0.1048-0.70342.97260.58723.12360.04270.2070.0402-0.0134-0.0052-0.09020.08240.0846-0.03750.0508-0.0034-0.01610.12580.01920.01084.7063-23.284212.7627
221.3439-3.81672.639910.08310.499719.4178-0.50021.13280.835-0.160.4687-0.1461-0.473-0.07870.03160.2554-0.02070.02610.16650.07380.061-1.7881-15.60895.2208
32.9398-1.61570.68534.7997-1.46533.4995-0.0205-0.148-0.06380.09940.00970.07220.3598-0.13130.01080.09350.001-0.00510.1463-0.03510.0131-1.9057-25.620337.3351
43.8263-1.3903-2.532817.09730.988416.4292-0.28260.5665-0.2559-0.70810.31340.37790.8391-0.4089-0.03080.2391-0.0092-0.08790.2672-0.0090.1236-2.2163-35.004228.7519
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A26 - 108
2X-RAY DIFFRACTION2B17 - 27
3X-RAY DIFFRACTION3C25 - 108
4X-RAY DIFFRACTION4D17 - 27

+
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