[English] 日本語
Yorodumi
- PDB-8p0d: Human 14-3-3 sigma in complex with human MDM2 peptide -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8p0d
TitleHuman 14-3-3 sigma in complex with human MDM2 peptide
Components
  • 14-3-3 protein sigma
  • E3 ubiquitin-protein ligase Mdm2
KeywordsPROTEIN BINDING / SIGNALING PROTEIN-PEPTIDE complex
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 / regulation of protein catabolic process at postsynapse, modulating synaptic transmission / fibroblast activation / 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 / regulation of protein catabolic process at postsynapse, modulating synaptic transmission / fibroblast activation / 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 / positive regulation of vascular associated smooth muscle cell migration / negative regulation of protein processing / SUMO transferase activity / response to steroid hormone / NEDD8 ligase activity / AKT phosphorylates targets in the cytosol / response to iron ion / atrioventricular valve morphogenesis / endocardial cushion morphogenesis / cellular response to peptide hormone stimulus / ventricular septum development / positive regulation of muscle cell differentiation / cardiac septum morphogenesis / regulation of postsynaptic neurotransmitter receptor internalization / regulation of epidermal cell division / blood vessel development / SUMOylation of ubiquitinylation proteins / protein kinase C inhibitor activity / ligase activity / positive regulation of epidermal cell differentiation / keratinocyte development / cellular response to alkaloid / keratinization / Constitutive Signaling by AKT1 E17K in Cancer / regulation of protein catabolic process / negative regulation of signal transduction by p53 class mediator / regulation of cell-cell adhesion / negative regulation of DNA damage response, signal transduction by p53 class mediator / SUMOylation of transcription factors / response to magnesium ion / cAMP/PKA signal transduction / Regulation of localization of FOXO transcription factors / cellular response to UV-C / protein sumoylation / keratinocyte proliferation / cellular response to actinomycin D / blood vessel remodeling / cellular response to estrogen stimulus / protein localization to nucleus / Activation of BAD and translocation to mitochondria / phosphoserine residue binding / negative regulation of keratinocyte proliferation / establishment of skin barrier / negative regulation of protein localization to plasma membrane / ribonucleoprotein complex binding / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / negative regulation of protein kinase activity / negative regulation of stem cell proliferation / protein autoubiquitination / positive regulation of vascular associated smooth muscle cell proliferation / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / RHO GTPases activate PKNs / positive regulation of protein localization / NPAS4 regulates expression of target genes / transcription repressor complex / positive regulation of cell adhesion / positive regulation of mitotic cell cycle / regulation of heart rate / protein sequestering activity / protein export from nucleus / negative regulation of innate immune response / proteolysis involved in protein catabolic process / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / release of cytochrome c from mitochondria / positive regulation of protein export from nucleus / ubiquitin binding / stem cell proliferation / response to cocaine / TP53 Regulates Metabolic Genes / Translocation of SLC2A4 (GLUT4) to the plasma membrane / DNA damage response, signal transduction by p53 class mediator / Stabilization of p53 / establishment of protein localization / Regulation of RUNX3 expression and activity / cellular response to gamma radiation / Oncogene Induced Senescence / RING-type E3 ubiquitin transferase / protein destabilization / Regulation of TP53 Activity through Methylation / cellular response to growth factor stimulus / response to toxic substance / centriolar satellite / cellular response to hydrogen peroxide / protein polyubiquitination / intrinsic apoptotic signaling pathway in response to DNA damage / ubiquitin-protein transferase activity / disordered domain specific binding
Similarity search - Function
E3 ubiquitin-protein ligase Mdm2 / MDM2, modified RING finger, HC subclass / p53 negative regulator Mdm2/Mdm4 / SWIB/MDM2 domain / SWIB/MDM2 domain / SWIB/MDM2 domain profile. / SWIB/MDM2 domain superfamily / Zn-finger in Ran binding protein and others / Zinc finger, C3HC4 type (RING finger) / Zinc finger RanBP2 type profile. ...E3 ubiquitin-protein ligase Mdm2 / MDM2, modified RING finger, HC subclass / p53 negative regulator Mdm2/Mdm4 / SWIB/MDM2 domain / SWIB/MDM2 domain / SWIB/MDM2 domain profile. / SWIB/MDM2 domain superfamily / Zn-finger in Ran binding protein and others / 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 / 14-3-3 protein sigma / 14-3-3 proteins signature 2. / 14-3-3 protein, conserved site / 14-3-3 proteins signature 1. / 14-3-3 protein / 14-3-3 homologues / 14-3-3 domain / 14-3-3 domain superfamily / 14-3-3 protein / Zinc finger RING-type profile. / Zinc finger, RING-type / Zinc finger, RING/FYVE/PHD-type
Similarity search - Domain/homology
DI(HYDROXYETHYL)ETHER / 14-3-3 protein sigma / E3 ubiquitin-protein ligase Mdm2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 1.31 Å
AuthorsRoversi, P. / Ward, J. / Doveston, R. / Kwon, H. / Romartinez Alonso, B.
Funding support United Kingdom, 5items
OrganizationGrant numberCountry
Wellcome Trust204801/Z/16/Z United Kingdom
Engineering and Physical Sciences Research CouncilEP/W015803/1 United Kingdom
Biotechnology and Biological Sciences Research Council (BBSRC)BB/S019456/1 United Kingdom
Biotechnology and Biological Sciences Research Council (BBSRC)BB/M01116X/1 United Kingdom
Wellcome Trust214090/Z/18/Z United Kingdom
CitationJournal: J.Biol.Chem. / Year: 2024
Title: Characterizing the protein-protein interaction between MDM2 and 14-3-3 sigma ; proof of concept for small molecule stabilization.
Authors: Ward, J.A. / Romartinez-Alonso, B. / Kay, D.F. / Bellamy-Carter, J. / Thurairajah, B. / Basran, J. / Kwon, H. / Leney, A.C. / Macip, S. / Roversi, P. / Muskett, F.W. / Doveston, R.G.
History
DepositionMay 10, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Feb 21, 2024Provider: repository / Type: Initial release
Revision 1.1Oct 16, 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: 14-3-3 protein sigma
B: E3 ubiquitin-protein ligase Mdm2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,6717
Polymers33,3892
Non-polymers2825
Water6,612367
1
A: 14-3-3 protein sigma
B: E3 ubiquitin-protein ligase Mdm2
hetero molecules

A: 14-3-3 protein sigma
B: E3 ubiquitin-protein ligase Mdm2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)67,34314
Polymers66,7784
Non-polymers56510
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation4_555x,-y,-z1
Buried area4810 Å2
ΔGint-58 kcal/mol
Surface area23630 Å2
MethodPISA
Unit cell
Length a, b, c (Å)82.588, 111.824, 62.551
Angle α, β, γ (deg.)90, 90, 90
Int Tables number20
Space group name H-MC2221

-
Components

-
Protein / Protein/peptide , 2 types, 2 molecules AB

#1: Protein 14-3-3 protein sigma / Epithelial cell marker protein 1 / Stratifin


Mass: 29549.094 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: TEV protease cleavable N-terminal His-tag. Cterm Delta-17 construct
Source: (gene. exp.) Homo sapiens (human) / Gene: SFN, HME1 / Plasmid: pPROEX Htb / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P31947
#2: Protein/peptide E3 ubiquitin-protein ligase Mdm2 / Double minute 2 protein / Hdm2 / Oncoprotein Mdm2 / RING-type E3 ubiquitin transferase Mdm2 / p53- ...Double minute 2 protein / Hdm2 / Oncoprotein Mdm2 / RING-type E3 ubiquitin transferase Mdm2 / p53-binding protein Mdm2


Mass: 3839.950 Da / Num. of mol.: 1 / Source method: obtained synthetically
Details: I modified this in order to be able to submit, but please correct the sequence of the peptide: RRRAI(SEP)ETEENSDELSGERQRKRHK(SEP)DSISL
Source: (synth.) Homo sapiens (human)
References: UniProt: Q00987, RING-type E3 ubiquitin transferase

-
Non-polymers , 5 types, 372 molecules

#3: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#4: Chemical ChemComp-PEG / DI(HYDROXYETHYL)ETHER


Mass: 106.120 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C4H10O3
#5: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Cl
#6: Chemical ChemComp-MG / MAGNESIUM ION


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


Mass: 18.015 Da / Num. of mol.: 367 / 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: 2.36 Å3/Da / Density % sol: 47.88 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.5
Details: 1 M HEPES pH 7.4 to 7.6, 0.19 M CaCl2, 30 to 31 % PEG 400, 5 % glycerol
PH range: 7.4 to 7.6

-
Data collection

DiffractionMean temperature: 100 K / Ambient temp details: Oxford Cryostream - 800 Series / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.91001 Å
DetectorType: DECTRIS EIGER2 X 16M / Detector: PIXEL / Date: Nov 27, 2021
RadiationMonochromator: double crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.91001 Å / Relative weight: 1
ReflectionResolution: 1.31→1.33 Å / Num. obs: 69740 / % possible obs: 100 % / Redundancy: 13.5 % / CC1/2: 0.998 / Rmerge(I) obs: 0.139 / Rpim(I) all: 0.039 / Rrim(I) all: 0.145 / Net I/σ(I): 9.7
Reflection shellResolution: 1.31→1.33 Å / Redundancy: 13.6 % / Rmerge(I) obs: 3.2 / Mean I/σ(I) obs: 0.5 / Num. unique obs: 3449 / CC1/2: 0.299 / Rpim(I) all: 0.892 / Rrim(I) all: 3.324 / % possible all: 99.7

-
Processing

Software
NameVersionClassification
BUSTER2.10.4refinement
xia23.8.dev0data reduction
DIALS3.dev.615-gfee771ddcdata scaling
BUSTER2.10.4phasing
RefinementMethod to determine structure: FOURIER SYNTHESIS / Resolution: 1.31→18.64 Å / Cor.coef. Fo:Fc: 0.966 / Cor.coef. Fo:Fc free: 0.961 / SU R Cruickshank DPI: 0.051 / Cross valid method: THROUGHOUT / SU R Blow DPI: 0.051 / SU Rfree Blow DPI: 0.054 / SU Rfree Cruickshank DPI: 0.05
RfactorNum. reflection% reflectionSelection details
Rfree0.2036 3384 -RANDOM
Rwork0.1775 ---
obs0.1788 69663 100 %-
Displacement parametersBiso mean: 22.95 Å2
Baniso -1Baniso -2Baniso -3
1--2.6563 Å20 Å20 Å2
2--0.8142 Å20 Å2
3---1.8421 Å2
Refine analyzeLuzzati coordinate error obs: 0.17 Å
Refinement stepCycle: LAST / Resolution: 1.31→18.64 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1912 0 16 367 2295
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0124203HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.177639HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1350SINUSOIDAL2
X-RAY DIFFRACTIONt_gen_planes699HARMONIC5
X-RAY DIFFRACTIONt_it4203HARMONIC10
X-RAY DIFFRACTIONt_chiral_improper_torsion285SEMIHARMONIC5
X-RAY DIFFRACTIONt_ideal_dist_contact4940SEMIHARMONIC4
X-RAY DIFFRACTIONt_omega_torsion4.66
X-RAY DIFFRACTIONt_other_torsion15.66
LS refinement shellResolution: 1.31→1.32 Å
RfactorNum. reflection% reflection
Rfree0.3331 75 -
Rwork0.3468 --
obs0.3461 1394 99.56 %
Refinement TLS params.

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)
10.2805-0.14340.11450.3325-0.12070.3632-0.0430.0402-0.04590.04020.03380.0452-0.04590.04520.0092-0.01880.0081-0.0007-0.0231-0.0059-0.014-23.89-16.66698.323
210.7128-1.75442.908621.20873.01684.54680.07310.0936-0.09970.09360.17640.3592-0.09970.3592-0.24940.02560.01970.01480.03120.04420.0524-14.3893-14.431510.2068
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{ A|* }A-3 - 231
2X-RAY DIFFRACTION1{ A|* }A301 - 302
3X-RAY DIFFRACTION2{ B|* }B164 - 187

+
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