[English] 日本語
Yorodumi
- PDB-7ad0: X-ray structure of Mdm2 with modified p53 peptide -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7ad0
TitleX-ray structure of Mdm2 with modified p53 peptide
Components
  • E3 ubiquitin-protein ligase Mdm2
  • Modified p53 peptide
KeywordsLIGASE / p53 / Mdm2 / MdmX / protein-protein interaction / inhibitor / cancer
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 / response to ether / 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 / traversing start control point of mitotic cell cycle / response to ether / 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 / SUMO transferase activity / negative regulation of protein processing / response to iron ion / response to steroid hormone / NEDD8 ligase activity / cellular response to peptide hormone stimulus / AKT phosphorylates targets in the cytosol / atrioventricular valve morphogenesis / ventricular septum development / endocardial cushion morphogenesis / positive regulation of muscle cell differentiation / cellular response to alkaloid / SUMOylation of ubiquitinylation proteins / regulation of protein catabolic process / blood vessel development / cardiac septum morphogenesis / ligase activity / Constitutive Signaling by AKT1 E17K in Cancer / negative regulation of DNA damage response, signal transduction by p53 class mediator / SUMOylation of transcription factors / response to magnesium ion / 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 / transcription repressor complex / NPAS4 regulates expression of target genes / regulation of heart rate / positive regulation of mitotic cell cycle / positive regulation of protein export from nucleus / proteolysis involved in protein catabolic process / ubiquitin binding / response to cocaine / Stabilization of p53 / Regulation of RUNX3 expression and activity / protein destabilization / establishment of protein localization / RING-type E3 ubiquitin transferase / Oncogene Induced Senescence / cellular response to gamma radiation / Regulation of TP53 Activity through Methylation / cellular response to growth factor stimulus / cellular response to hydrogen peroxide / response to toxic substance / protein polyubiquitination / ubiquitin-protein transferase activity / disordered domain specific binding / endocytic vesicle membrane / ubiquitin protein ligase activity / p53 binding / Signaling by ALK fusions and activated point mutants / Regulation of TP53 Degradation / negative regulation of neuron projection development / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / 5S rRNA binding / cellular response to hypoxia / ubiquitin-dependent protein catabolic process / regulation of gene expression / protein-containing complex assembly / Oxidative Stress Induced Senescence / proteasome-mediated ubiquitin-dependent protein catabolic process / Regulation of TP53 Activity through Phosphorylation / amyloid fibril formation / regulation of cell cycle / Ub-specific processing proteases / protein ubiquitination / response to xenobiotic stimulus / protein domain specific binding / response to antibiotic / negative regulation of DNA-templated transcription / ubiquitin protein ligase binding / positive regulation of cell population proliferation / positive regulation of gene expression / negative regulation of apoptotic process / nucleolus / apoptotic process / negative regulation of transcription by RNA polymerase II / enzyme binding / protein-containing complex / zinc ion binding / nucleoplasm
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
E3 ubiquitin-protein ligase Mdm2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.07 Å
AuthorsTwarda-Clapa, A. / Fortuna, P. / Grudnik, P. / Dubin, G. / Berlicki, L. / Holak, T.A.
CitationJournal: Eur.J.Med.Chem. / Year: 2020
Title: Systematic ""foldamerization"" of peptide inhibiting p53-MDM2/X interactions by the incorporation of trans- or cis-2-aminocyclopentanecarboxylic acid residues
Authors: Fortuna, P. / Twarda-Clapa, A. / Skalniak, L. / Ozga, K. / Holak, T.A. / Berlicki, L.
History
DepositionSep 13, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 28, 2020Provider: repository / Type: Initial release
Revision 1.1Oct 26, 2022Group: Database references / Category: citation / database_2
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.title / _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 2.0Nov 15, 2023Group: Atomic model / Data collection / Derived calculations
Category: atom_site / atom_site_anisotrop ...atom_site / atom_site_anisotrop / chem_comp_atom / chem_comp_bond / pdbx_validate_main_chain_plane / pdbx_validate_rmsd_angle / struct_conn
Item: _atom_site.auth_atom_id / _atom_site.label_atom_id ..._atom_site.auth_atom_id / _atom_site.label_atom_id / _atom_site_anisotrop.pdbx_auth_atom_id / _atom_site_anisotrop.pdbx_label_atom_id / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr2_label_atom_id
Revision 2.1Jan 31, 2024Group: Refinement description / Category: pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: E3 ubiquitin-protein ligase Mdm2
B: E3 ubiquitin-protein ligase Mdm2
C: E3 ubiquitin-protein ligase Mdm2
D: E3 ubiquitin-protein ligase Mdm2
E: E3 ubiquitin-protein ligase Mdm2
F: E3 ubiquitin-protein ligase Mdm2
H: Modified p53 peptide
I: Modified p53 peptide
J: Modified p53 peptide
K: Modified p53 peptide
L: Modified p53 peptide
M: Modified p53 peptide


Theoretical massNumber of molelcules
Total (without water)73,16012
Polymers73,16012
Non-polymers00
Water2,972165
1
A: E3 ubiquitin-protein ligase Mdm2
H: Modified p53 peptide


Theoretical massNumber of molelcules
Total (without water)12,1932
Polymers12,1932
Non-polymers00
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1210 Å2
ΔGint-11 kcal/mol
Surface area6090 Å2
MethodPISA
2
B: E3 ubiquitin-protein ligase Mdm2
I: Modified p53 peptide


Theoretical massNumber of molelcules
Total (without water)12,1932
Polymers12,1932
Non-polymers00
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1190 Å2
ΔGint-12 kcal/mol
Surface area6170 Å2
MethodPISA
3
C: E3 ubiquitin-protein ligase Mdm2
J: Modified p53 peptide


Theoretical massNumber of molelcules
Total (without water)12,1932
Polymers12,1932
Non-polymers00
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1200 Å2
ΔGint-11 kcal/mol
Surface area5830 Å2
MethodPISA
4
D: E3 ubiquitin-protein ligase Mdm2
K: Modified p53 peptide


Theoretical massNumber of molelcules
Total (without water)12,1932
Polymers12,1932
Non-polymers00
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1200 Å2
ΔGint-12 kcal/mol
Surface area6090 Å2
MethodPISA
5
E: E3 ubiquitin-protein ligase Mdm2
L: Modified p53 peptide


Theoretical massNumber of molelcules
Total (without water)12,1932
Polymers12,1932
Non-polymers00
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1200 Å2
ΔGint-12 kcal/mol
Surface area5980 Å2
MethodPISA
6
F: E3 ubiquitin-protein ligase Mdm2
M: Modified p53 peptide


Theoretical massNumber of molelcules
Total (without water)12,1932
Polymers12,1932
Non-polymers00
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1170 Å2
ΔGint-11 kcal/mol
Surface area6010 Å2
MethodPISA
Unit cell
Length a, b, c (Å)46.811, 76.082, 197.299
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
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: 10642.509 Da / Num. of mol.: 6
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MDM2 / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: Q00987, RING-type E3 ubiquitin transferase
#2: Protein/peptide
Modified p53 peptide


Mass: 1550.751 Da / Num. of mol.: 6 / Source method: obtained synthetically
Details: This short chain is a modified p53 peptide. 475 is a modified aminoacid that was introduced to this chemically synthesized peptide to increase the affinity to Mdm2. N- and C-terminal ...Details: This short chain is a modified p53 peptide. 475 is a modified aminoacid that was introduced to this chemically synthesized peptide to increase the affinity to Mdm2. N- and C-terminal alanines in this peptide are the terminal modifications: acetyl group at the N-terminus, and amide group at the C-terminus.
Source: (synth.) Homo sapiens (human)
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 165 / 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: 2.36 Å3/Da / Density % sol: 47.94 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 5.5
Details: 0.1 M Bis-Tris pH 5.5 with 0.2 M NaCl and 25% PEG 3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: BESSY / Beamline: 14.1 / Wavelength: 0.97 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Dec 3, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97 Å / Relative weight: 1
ReflectionResolution: 2.07→49.33 Å / Num. obs: 43882 / % possible obs: 99.5 % / Redundancy: 13.12 % / Rrim(I) all: 0.115 / Net I/σ(I): 16.98
Reflection shellResolution: 2.07→2.144 Å / Num. unique obs: 4309 / Rrim(I) all: 1.318

-
Processing

Software
NameVersionClassification
REFMAC5.8.0049refinement
PDB_EXTRACT3.22data extraction
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3TJ2

3tj2


Resolution: 2.07→49.32 Å / Cor.coef. Fo:Fc: 0.967 / Cor.coef. Fo:Fc free: 0.946 / SU B: 13.692 / SU ML: 0.169 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.194 / ESU R Free: 0.176 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.2385 2100 4.8 %RANDOM
Rwork0.1871 ---
obs0.1895 41868 99.47 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 122.29 Å2 / Biso mean: 49.976 Å2 / Biso min: 17.22 Å2
Baniso -1Baniso -2Baniso -3
1-4.41 Å2-0 Å20 Å2
2--0.74 Å20 Å2
3----5.14 Å2
Refinement stepCycle: final / Resolution: 2.07→49.32 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4960 0 0 165 5125
Biso mean---46.1 -
Num. residues----608
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0150.025096
X-RAY DIFFRACTIONr_bond_other_d0.0010.025061
X-RAY DIFFRACTIONr_angle_refined_deg1.7992.0036891
X-RAY DIFFRACTIONr_angle_other_deg1.267311654
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.9615584
X-RAY DIFFRACTIONr_dihedral_angle_2_deg44.52223.46211
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.83815952
X-RAY DIFFRACTIONr_dihedral_angle_4_deg24.4071524
X-RAY DIFFRACTIONr_chiral_restr0.150.2786
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.025470
X-RAY DIFFRACTIONr_gen_planes_other0.0010.021152
LS refinement shellResolution: 2.07→2.12 Å / Rfactor Rfree error: 0
RfactorNum. reflection% reflection
Rfree0.325 148 -
Rwork0.329 2965 -
obs--96.02 %
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)
11.9335-0.3615-0.89923.2872-0.10572.66130.2530.33180.3831-0.2903-0.0340.1641-0.5325-0.4576-0.21890.24990.14320.03320.26910.08810.2564-4.35221.9377-27.2373
21.3587-0.72460.49943.4957-0.99392.77580.0110.00140.13880.0169-0.0062-0.08790.0117-0.0499-0.00480.0011-0.01230.00210.18730.01660.185216.5044-15.6474-27.1496
32.3380.6551-1.27511.74220.86534.28990.0869-0.1228-0.01490.49820.2729-0.34130.5090.6111-0.35980.21990.1303-0.09110.199-0.04350.210317.188734.8629-39.1267
42.06250.53440.58561.6238-0.96922.8265-0.0264-0.0875-0.01180.03020.13620.03820.0416-0.1686-0.10970.05330.02390.0170.19310.02140.2266-6.8184-4.865-37.7168
51.33791.3814-0.07373.286-1.01862.5011-0.05480.1873-0.0342-0.3580.0422-0.11520.2257-0.05550.01260.17530.05710.020.16150.00890.1556-2.807-12.54335.1294
61.17680.15210.24443.5247-1.36823.82430.0731-0.19250.00460.4383-0.1451-0.2495-0.39150.04450.0720.1456-0.026-0.0190.15980.00640.16762.2712.2655-5.7415
73.7122.46531.50792.26911.81014.27060.22850.34170.08660.1085-0.1414-0.2548-0.32650.0268-0.08710.12160.00620.01820.34120.16310.29285.467915.9586-22.3939
81.7505-2.78470.12394.5468-0.75378.145-0.04240.14810.2270.1675-0.1557-0.4282-0.02630.33590.19810.1340.0572-0.05090.2732-0.00160.249525.876-21.6232-21.4586
93.74361.5994-1.35745.32740.96977.7705-0.06180.11130.40870.50860.2786-0.0432-0.3257-0.0035-0.21680.11750.04270.00730.12850.00730.18097.28539.638-44.4882
104.8861.78941.60233.31530.70265.5188-0.3435-0.32360.32420.19240.35670.3292-0.2467-0.3496-0.01320.07580.0730.02650.17290.05450.2214-15.26432.3521-43.2999
115.94014.846-1.03584.8607-1.70791.0676-0.0323-0.1592-0.3107-0.5277-0.1267-0.34040.44410.08030.1590.307-0.01260.06330.1586-0.00260.1843-1.7669-23.589410.6367
123.8976-2.6517-1.04415.4673-0.28026.53570.1277-0.03410.6730.5141-0.3135-0.523-0.69570.35790.18580.3732-0.04360.00240.2153-0.02550.32982.852723.2936-11.3235
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A24 - 113
2X-RAY DIFFRACTION2B25 - 111
3X-RAY DIFFRACTION3C25 - 110
4X-RAY DIFFRACTION4D25 - 111
5X-RAY DIFFRACTION5E25 - 111
6X-RAY DIFFRACTION6F25 - 111
7X-RAY DIFFRACTION7H16 - 29
8X-RAY DIFFRACTION8I16 - 29
9X-RAY DIFFRACTION9J16 - 29
10X-RAY DIFFRACTION10K16 - 29
11X-RAY DIFFRACTION11L16 - 29
12X-RAY DIFFRACTION12M16 - 29

+
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