[English] 日本語
Yorodumi
- PDB-7bj0: Inhibitor of MDM2-p53 Interaction -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7bj0
TitleInhibitor of MDM2-p53 Interaction
ComponentsE3 ubiquitin-protein ligase Mdm2
KeywordsAPOPTOSIS / ligase / cell cycle / protein binding
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 / negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator / 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 / response to ether / traversing start control point of mitotic cell cycle / negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator / 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 / response to iron ion / negative regulation of protein processing / SUMO transferase activity / response to steroid hormone / NEDD8 ligase activity / AKT phosphorylates targets in the cytosol / cellular response to peptide hormone stimulus / atrioventricular valve morphogenesis / ventricular septum development / endocardial cushion morphogenesis / cellular response to alkaloid / positive regulation of muscle cell differentiation / SUMOylation of ubiquitinylation proteins / blood vessel development / regulation of protein catabolic process / cardiac septum morphogenesis / Constitutive Signaling by AKT1 E17K in Cancer / negative regulation of DNA damage response, signal transduction by p53 class mediator / response to magnesium ion / protein sumoylation / ligase activity / SUMOylation of transcription factors / protein localization to nucleus / cellular response to actinomycin D / cellular response to UV-C / blood vessel remodeling / cellular response to estrogen stimulus / protein autoubiquitination / ribonucleoprotein complex binding / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / positive regulation of vascular associated smooth muscle cell proliferation / transcription repressor complex / NPAS4 regulates expression of target genes / regulation of heart rate / proteolysis involved in protein catabolic process / positive regulation of mitotic cell cycle / positive regulation of protein export from nucleus / response to cocaine / ubiquitin binding / Stabilization of p53 / Regulation of RUNX3 expression and activity / protein destabilization / RING-type E3 ubiquitin transferase / cellular response to gamma radiation / establishment of protein localization / Oncogene Induced Senescence / Regulation of TP53 Activity through Methylation / response to toxic substance / cellular response to hydrogen peroxide / cellular response to growth factor stimulus / protein polyubiquitination / ubiquitin-protein transferase activity / endocytic vesicle membrane / ubiquitin protein ligase activity / disordered domain specific binding / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Regulation of TP53 Degradation / p53 binding / negative regulation of neuron projection development / 5S rRNA binding / ubiquitin-dependent protein catabolic process / cellular response to hypoxia / proteasome-mediated ubiquitin-dependent protein catabolic process / regulation of gene expression / protein-containing complex assembly / Oxidative Stress Induced Senescence / Regulation of TP53 Activity through Phosphorylation / amyloid fibril formation / protein ubiquitination / regulation of cell cycle / Ub-specific processing proteases / 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 / negative regulation of transcription by RNA polymerase II / enzyme binding / protein-containing complex / zinc ion binding / nucleoplasm / identical protein 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 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
Similarity search - Domain/homology
Chem-TVH / E3 ubiquitin-protein ligase Mdm2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2 Å
AuthorsWilliams, P.A.
CitationJournal: J.Med.Chem. / Year: 2021
Title: Structure-Based Design of Potent and Orally Active Isoindolinone Inhibitors of MDM2-p53 Protein-Protein Interaction.
Authors: Chessari, G. / Hardcastle, I.R. / Ahn, J.S. / Anil, B. / Anscombe, E. / Bawn, R.H. / Bevan, L.D. / Blackburn, T.J. / Buck, I. / Cano, C. / Carbain, B. / Castro, J. / Cons, B. / Cully, S.J. / ...Authors: Chessari, G. / Hardcastle, I.R. / Ahn, J.S. / Anil, B. / Anscombe, E. / Bawn, R.H. / Bevan, L.D. / Blackburn, T.J. / Buck, I. / Cano, C. / Carbain, B. / Castro, J. / Cons, B. / Cully, S.J. / Endicott, J.A. / Fazal, L. / Golding, B.T. / Griffin, R.J. / Haggerty, K. / Harnor, S.J. / Hearn, K. / Hobson, S. / Holvey, R.S. / Howard, S. / Jennings, C.E. / Johnson, C.N. / Lunec, J. / Miller, D.C. / Newell, D.R. / Noble, M.E.M. / Reeks, J. / Revill, C.H. / Riedinger, C. / St Denis, J.D. / Tamanini, E. / Thomas, H. / Thompson, N.T. / Vinkovic, M. / Wedge, S.R. / Williams, P.A. / Wilsher, N.E. / Zhang, B. / Zhao, Y.
History
DepositionJan 13, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 7, 2021Provider: repository / Type: Initial release
Revision 2.0Apr 21, 2021Group: Advisory / Atomic model ...Advisory / Atomic model / Data collection / Database references / Derived calculations / Experimental preparation / Non-polymer description / Polymer sequence / Source and taxonomy / Structure summary
Category: atom_site / atom_site_anisotrop ...atom_site / atom_site_anisotrop / chem_comp / citation / citation_author / diffrn_radiation_wavelength / entity / entity_poly / entity_poly_seq / entity_src_gen / exptl_crystal / pdbx_poly_seq_scheme / pdbx_struct_sheet_hbond / pdbx_unobs_or_zero_occ_residues / struct_conf / struct_ref / struct_ref_seq / struct_ref_seq_dif / struct_sheet_range / struct_site_gen
Item: _atom_site.label_seq_id / _atom_site_anisotrop.pdbx_label_seq_id ..._atom_site.label_seq_id / _atom_site_anisotrop.pdbx_label_seq_id / _chem_comp.formula / _chem_comp.formula_weight / _chem_comp.id / _chem_comp.mon_nstd_flag / _chem_comp.name / _chem_comp.type / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID / _diffrn_radiation_wavelength.wavelength / _entity.formula_weight / _entity.pdbx_description / _entity.pdbx_ec / _entity_poly.pdbx_seq_one_letter_code / _entity_poly.pdbx_seq_one_letter_code_can / _exptl_crystal.density_Matthews / _exptl_crystal.density_percent_sol / _pdbx_struct_sheet_hbond.range_1_label_seq_id / _pdbx_struct_sheet_hbond.range_2_label_seq_id / _struct_conf.beg_label_seq_id / _struct_conf.end_label_seq_id / _struct_sheet_range.beg_label_seq_id / _struct_sheet_range.end_label_seq_id / _struct_site_gen.label_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: E3 ubiquitin-protein ligase Mdm2
B: E3 ubiquitin-protein ligase Mdm2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)26,8044
Polymers25,7772
Non-polymers1,0272
Water2,594144
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4750 Å2
ΔGint-27 kcal/mol
Surface area10660 Å2
MethodPISA
Unit cell
Length a, b, c (Å)96.538, 96.538, 72.984
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number152
Space group name H-MP3121

-
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: 12888.703 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MDM2 / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): pLysS
References: UniProt: Q00987, RING-type E3 ubiquitin transferase
#2: Chemical ChemComp-TVH / (3~{R})-4-chloranyl-3-(4-chlorophenyl)-3-[[1-(hydroxymethyl)cyclopropyl]methoxy]-2-[(4-nitrophenyl)methyl]isoindol-1-one


Mass: 513.369 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C26H22Cl2N2O5 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 144 / 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: 3.81 Å3/Da / Density % sol: 67.7 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / Details: 2.2M (NH4)2SO4

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 1.0719 Å
DetectorType: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Aug 8, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.0719 Å / Relative weight: 1
ReflectionResolution: 2→83.6 Å / Num. obs: 25478 / % possible obs: 95.5 % / Redundancy: 6.3 % / Rmerge(I) obs: 0.082 / Net I/σ(I): 9
Reflection shellResolution: 2→2.05 Å / Rmerge(I) obs: 0.914 / Num. unique obs: 1925

-
Processing

Software
NameVersionClassification
REFMAC5.8.0222refinement
PDB_EXTRACT3.27data extraction
XDSdata reduction
Aimlessdata scaling
REFMACphasing
RefinementMethod to determine structure: FOURIER SYNTHESIS / Resolution: 2→83.6 Å / Cor.coef. Fo:Fc: 0.967 / Cor.coef. Fo:Fc free: 0.961 / SU B: 8.881 / SU ML: 0.127 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.13 / ESU R Free: 0.119 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: U VALUES : WITH TLS ADDED HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.2111 1293 5.1 %RANDOM
Rwork0.194 ---
obs0.1949 24168 94.63 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 120.32 Å2 / Biso mean: 60.398 Å2 / Biso min: 36.97 Å2
Baniso -1Baniso -2Baniso -3
1-0 Å20 Å20 Å2
2--0 Å2-0 Å2
3----0 Å2
Refinement stepCycle: final / Resolution: 2→83.6 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1527 0 112 144 1783
Biso mean--51.8 62.66 -
Num. residues----187
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0151684
X-RAY DIFFRACTIONr_bond_other_d0.0010.0171564
X-RAY DIFFRACTIONr_angle_refined_deg1.3071.7312300
X-RAY DIFFRACTIONr_angle_other_deg0.4341.693669
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.8655201
X-RAY DIFFRACTIONr_dihedral_angle_2_deg41.04221.38565
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.35215286
X-RAY DIFFRACTIONr_dihedral_angle_4_deg11.003158
X-RAY DIFFRACTIONr_chiral_restr0.0640.2210
X-RAY DIFFRACTIONr_gen_planes_refined0.0030.0221829
X-RAY DIFFRACTIONr_gen_planes_other00.02311
LS refinement shellResolution: 2→2.052 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.355 97 -
Rwork0.369 1813 -
all-1910 -
obs--96.71 %
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)
13.95940.72363.1451.5661.34754.97090.30280.2948-0.09770.01310.0104-0.1277-0.16250.5759-0.31320.2349-0.05520.07710.0885-0.02650.4944-41.67129.4258-10.4095
22.7385-0.13222.44241.0446-0.58164.2130.22640.1092-0.0433-0.0832-0.09610.0631-0.170.0002-0.13030.26360.04650.0340.0235-0.02280.4701-53.52039.0695-16.1305
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A17 - 109
2X-RAY DIFFRACTION2B17 - 110

+
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