[English] 日本語
Yorodumi
- PDB-6y4q: Structure of a stapled peptide bound to MDM2 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6y4q
TitleStructure of a stapled peptide bound to MDM2
Components
  • ACE-LEU-THR-PHE-GLY-GLU-TYR-TRP-ALA-GLN-LEU-ALA-SER
  • E3 ubiquitin-protein ligase Mdm2
KeywordsLIGASE / MDM2 / p53 / stapled
Function / homology
Function and homology information


cellular response to vitamin B1 / response to formaldehyde / response to water-immersion restraint stress / traversing start control point of mitotic cell cycle / negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator / response to ether / negative regulation of signal transduction by p53 class mediator / fibroblast activation / atrial septum development / receptor serine/threonine kinase binding ...cellular response to vitamin B1 / response to formaldehyde / response to water-immersion restraint stress / traversing start control point of mitotic cell cycle / negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator / response to ether / negative regulation of signal transduction by p53 class mediator / fibroblast activation / atrial septum development / receptor serine/threonine kinase binding / Trafficking of AMPA receptors / positive regulation of vascular associated smooth muscle cell migration / peroxisome proliferator activated receptor binding / SUMO transferase activity / negative regulation of protein processing / response to iron ion / response to steroid hormone / NEDD8 ligase activity / AKT phosphorylates targets in the cytosol / atrioventricular valve morphogenesis / cellular response to peptide hormone stimulus / ventricular septum development / endocardial cushion morphogenesis / positive regulation of muscle cell differentiation / SUMOylation of ubiquitinylation proteins / cellular response to alkaloid / blood vessel development / regulation of protein catabolic process / cardiac septum morphogenesis / Constitutive Signaling by AKT1 E17K in Cancer / ligase activity / negative regulation of DNA damage response, signal transduction by p53 class mediator / response to magnesium ion / SUMOylation of transcription factors / protein sumoylation / protein localization to nucleus / cellular response to UV-C / blood vessel remodeling / cellular response to estrogen stimulus / protein autoubiquitination / cellular response to actinomycin D / ribonucleoprotein complex binding / positive regulation of vascular associated smooth muscle cell proliferation / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / NPAS4 regulates expression of target genes / transcription repressor complex / regulation of heart rate / positive regulation of mitotic cell cycle / positive regulation of protein export from nucleus / response to cocaine / proteolysis involved in protein catabolic process / ubiquitin binding / Stabilization of p53 / Regulation of RUNX3 expression and activity / protein destabilization / RING-type E3 ubiquitin transferase / establishment of protein localization / Oncogene Induced Senescence / Regulation of TP53 Activity through Methylation / response to toxic substance / cellular response to gamma radiation / cellular response to growth factor stimulus / cellular response to hydrogen peroxide / protein polyubiquitination / ubiquitin-protein transferase activity / endocytic vesicle membrane / ubiquitin protein ligase activity / disordered domain specific binding / Signaling by ALK fusions and activated point mutants / Regulation of TP53 Degradation / p53 binding / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / negative regulation of neuron projection development / cellular response to hypoxia / 5S rRNA binding / ubiquitin-dependent protein catabolic process / regulation of gene expression / protein-containing complex assembly / proteasome-mediated ubiquitin-dependent protein catabolic process / Oxidative Stress Induced Senescence / Regulation of TP53 Activity through Phosphorylation / amyloid fibril formation / Ub-specific processing proteases / regulation of cell cycle / protein ubiquitination / response to xenobiotic stimulus / protein domain specific binding / response to antibiotic / negative regulation of DNA-templated transcription / apoptotic process / ubiquitin protein ligase binding / positive regulation of cell population proliferation / positive regulation of gene expression / nucleolus / negative regulation of apoptotic process / enzyme binding / negative regulation of transcription by RNA polymerase II / protein-containing complex / zinc ion binding / nucleoplasm
Similarity search - Function
MDM2 / SWIB/MDM2 domain / 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 ...MDM2 / SWIB/MDM2 domain / 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 signature. / Zinc finger, RanBP2-type superfamily / Zinc finger, RanBP2-type / Zinc finger RING-type profile. / Zinc finger, RING-type / Zinc finger, RING/FYVE/PHD-type / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-O9E / E3 ubiquitin-protein ligase Mdm2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.63 Å
AuthorsPantelejevs, T. / Bakanovych, I.
Funding support United Kingdom, 1items
OrganizationGrant numberCountry
Medical Research Council (MRC, United Kingdom) United Kingdom
CitationJournal: Org.Biomol.Chem. / Year: 2020
Title: Diarylethene moiety as an enthalpy-entropy switch: photoisomerizable stapled peptides for modulating p53/MDM2 interaction.
Authors: Strizhak, A.V. / Babii, O. / Afonin, S. / Bakanovich, I. / Pantelejevs, T. / Xu, W. / Fowler, E. / Eapen, R. / Sharma, K. / Platonov, M.O. / Hurmach, V.V. / Itzhaki, L. / Hyvonen, M. / ...Authors: Strizhak, A.V. / Babii, O. / Afonin, S. / Bakanovich, I. / Pantelejevs, T. / Xu, W. / Fowler, E. / Eapen, R. / Sharma, K. / Platonov, M.O. / Hurmach, V.V. / Itzhaki, L. / Hyvonen, M. / Ulrich, A.S. / Spring, D.R. / Komarov, I.V.
History
DepositionFeb 22, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0May 20, 2020Provider: repository / Type: Initial release
Revision 1.1Jul 29, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2Jan 24, 2024Group: Advisory / Data collection ...Advisory / Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_unobs_or_zero_occ_atoms
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: E3 ubiquitin-protein ligase Mdm2
B: E3 ubiquitin-protein ligase Mdm2
C: ACE-LEU-THR-PHE-GLY-GLU-TYR-TRP-ALA-GLN-LEU-ALA-SER
D: ACE-LEU-THR-PHE-GLY-GLU-TYR-TRP-ALA-GLN-LEU-ALA-SER
hetero molecules


Theoretical massNumber of molelcules
Total (without water)25,3786
Polymers24,1644
Non-polymers1,2142
Water2,270126
1
A: E3 ubiquitin-protein ligase Mdm2
C: ACE-LEU-THR-PHE-GLY-GLU-TYR-TRP-ALA-GLN-LEU-ALA-SER
hetero molecules


Theoretical massNumber of molelcules
Total (without water)12,6893
Polymers12,0822
Non-polymers6071
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1510 Å2
ΔGint-11 kcal/mol
Surface area5990 Å2
MethodPISA
2
B: E3 ubiquitin-protein ligase Mdm2
D: ACE-LEU-THR-PHE-GLY-GLU-TYR-TRP-ALA-GLN-LEU-ALA-SER
hetero molecules


Theoretical massNumber of molelcules
Total (without water)12,6893
Polymers12,0822
Non-polymers6071
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1460 Å2
ΔGint-11 kcal/mol
Surface area5980 Å2
MethodPISA
Unit cell
Length a, b, c (Å)34.240, 34.840, 48.410
Angle α, β, γ (deg.)93.380, 107.380, 117.450
Int Tables number1
Space group name H-MP1

-
Components

#1: Protein 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: 10670.497 Da / Num. of mol.: 2 / Mutation: E69A, K70A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MDM2 / Production host: Escherichia coli BL21 (bacteria)
References: UniProt: Q00987, RING-type E3 ubiquitin transferase
#2: Protein/peptide ACE-LEU-THR-PHE-GLY-GLU-TYR-TRP-ALA-GLN-LEU-ALA-SER


Mass: 1411.558 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human)
#3: Chemical ChemComp-O9E / ~{N}-[(1-ethyl-1,2,3-triazol-4-yl)methyl]-~{N},5-dimethyl-4-[2-[2-methyl-5-[methyl-[(1-propyl-1,2,3-triazol-4-yl)methyl]carbamoyl]thiophen-3-yl]cyclopenten-1-yl]thiophene-2-carboxamide


Mass: 606.805 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C30H38N8O2S2 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 126 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 1.97 Å3/Da / Density % sol: 37.52 %
Crystal growTemperature: 291 K / Method: vapor diffusion
Details: 10% w/v PEG 8000 (precipitant), 0.1 M Tris-HCl pH 7.0 (buffer), 0.2 M Magnesium chloride hexahydrate (salt)

-
Data collection

DiffractionMean temperature: 63 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.9762 Å
DetectorType: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Dec 2, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9762 Å / Relative weight: 1
ReflectionResolution: 1.63→44.93 Å / Num. obs: 21777 / % possible obs: 94.9 % / Redundancy: 3 % / Biso Wilson estimate: 24.98 Å2 / CC1/2: 0.987 / Rmerge(I) obs: 0.162 / Rpim(I) all: 0.087 / Rrim(I) all: 0.184 / Net I/σ(I): 23.3 / Num. measured all: 65928 / Scaling rejects: 8
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
1.63-1.721.70.462514829650.7120.4620.6544.488.6
5.16-44.935.10.14836827230.9830.0720.16560.199.9

-
Processing

Software
NameVersionClassification
Aimless0.5.31data scaling
BUSTERrefinement
PDB_EXTRACT3.25data extraction
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5AFG

5afg


Resolution: 1.63→30.07 Å / Cor.coef. Fo:Fc: 0.948 / Cor.coef. Fo:Fc free: 0.93 / SU R Cruickshank DPI: 0.123 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.121 / SU Rfree Blow DPI: 0.113 / SU Rfree Cruickshank DPI: 0.115
RfactorNum. reflection% reflectionSelection details
Rfree0.229 1086 4.99 %RANDOM
Rwork0.194 ---
obs0.196 21751 94.8 %-
Displacement parametersBiso max: 155.24 Å2 / Biso mean: 30.76 Å2 / Biso min: 10.94 Å2
Baniso -1Baniso -2Baniso -3
1--0.9699 Å2-4.639 Å20.5338 Å2
2---3.8332 Å23.3769 Å2
3---4.8031 Å2
Refine analyzeLuzzati coordinate error obs: 0.24 Å
Refinement stepCycle: final / Resolution: 1.63→30.07 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1704 0 84 126 1914
Biso mean--40.22 44.24 -
Num. residues----209
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d691SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes384HARMONIC5
X-RAY DIFFRACTIONt_it1938HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion233SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact2541SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d1938HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg2640HARMONIC20.97
X-RAY DIFFRACTIONt_omega_torsion3.38
X-RAY DIFFRACTIONt_other_torsion18.98
LS refinement shellResolution: 1.63→1.64 Å / Rfactor Rfree error: 0 / Total num. of bins used: 50
RfactorNum. reflection% reflection
Rfree0.3857 17 3.9 %
Rwork0.2815 419 -
all0.2852 436 -
obs--84.8 %

+
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://pdbjlvh1.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