[English] 日本語
Yorodumi
- PDB-3tpx: Crystal structure of human MDM2 in complex with a trifluoromethyl... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3tpx
TitleCrystal structure of human MDM2 in complex with a trifluoromethylated D-peptide inhibitor
Components
  • D-peptide inhibitor DPMI-delta
  • E3 ubiquitin-protein ligase Mdm2
KeywordsLIGASE/LIGASE INHIBITOR / LIGASE-LIGASE INHIBITOR complex / MDM2-D-peptide inhibitor complex / p53-binding domain of MDM2-D-peptide inhibitor complex
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
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
D-peptide inhibitor DPMI-delta / ACETATE ION / polypeptide(D) / polypeptide(D) (> 10) / E3 ubiquitin-protein ligase Mdm2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.8 Å
AuthorsWu, X. / Pazgier, M.
CitationJournal: J.Med.Chem. / Year: 2012
Title: An Ultrahigh Affinity d-Peptide Antagonist Of MDM2.
Authors: Zhan, C. / Zhao, L. / Wei, X. / Wu, X. / Chen, X. / Yuan, W. / Lu, W.Y. / Pazgier, M. / Lu, W.
History
DepositionSep 8, 2011Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 20, 2012Provider: repository / Type: Initial release
Revision 1.1Jun 27, 2012Group: Database references
Revision 1.2Jul 25, 2012Group: Database references
Revision 1.3Dec 12, 2012Group: Other
Revision 1.4Jun 19, 2013Group: Structure summary
Revision 1.5Sep 13, 2023Group: 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 / pdbx_initial_refinement_model / struct_conn / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_leaving_atom_flag / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.6Dec 6, 2023Group: Data collection / Derived calculations / Category: chem_comp_atom / chem_comp_bond / struct_conn
Item: _chem_comp_atom.atom_id / _chem_comp_bond.atom_id_2 / _struct_conn.pdbx_leaving_atom_flag

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: E3 ubiquitin-protein ligase Mdm2
B: D-peptide inhibitor DPMI-delta
C: E3 ubiquitin-protein ligase Mdm2
D: D-peptide inhibitor DPMI-delta
E: E3 ubiquitin-protein ligase Mdm2
F: D-peptide inhibitor DPMI-delta
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,57818
Polymers34,8776
Non-polymers70212
Water4,053225
1
A: E3 ubiquitin-protein ligase Mdm2
B: D-peptide inhibitor DPMI-delta
hetero molecules


Theoretical massNumber of molelcules
Total (without water)11,7223
Polymers11,6262
Non-polymers961
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1660 Å2
ΔGint-21 kcal/mol
Surface area5890 Å2
MethodPISA
2
C: E3 ubiquitin-protein ligase Mdm2
D: D-peptide inhibitor DPMI-delta
hetero molecules


Theoretical massNumber of molelcules
Total (without water)12,0669
Polymers11,6262
Non-polymers4407
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1920 Å2
ΔGint-29 kcal/mol
Surface area5670 Å2
MethodPISA
3
E: E3 ubiquitin-protein ligase Mdm2
F: D-peptide inhibitor DPMI-delta
hetero molecules


Theoretical massNumber of molelcules
Total (without water)11,7916
Polymers11,6262
Non-polymers1654
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1640 Å2
ΔGint-30 kcal/mol
Surface area5950 Å2
MethodPISA
Unit cell
Length a, b, c (Å)70.532, 211.811, 45.327
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number20
Space group name H-MC2221
Components on special symmetry positions
IDModelComponents
11A-392-

HOH

21C-346-

HOH

31E-351-

HOH

-
Components

-
Protein / Polypeptide(D) , 2 types, 6 molecules ACEBDF

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


Mass: 10044.889 Da / Num. of mol.: 3 / Fragment: p53 binding domain (UNP residues 25-109) / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human)
References: UniProt: Q00987, Ligases; Forming carbon-nitrogen bonds; Acid-amino-acid ligases (peptide synthases)
#2: Polypeptide(D) D-peptide inhibitor DPMI-delta


Type: Peptide-like / Class: Inhibitor / Mass: 1580.729 Da / Num. of mol.: 3 / Source method: obtained synthetically / References: D-peptide inhibitor DPMI-delta

-
Non-polymers , 4 types, 237 molecules

#3: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: SO4
#4: Chemical
ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: Cl
#5: Chemical
ChemComp-ACT / ACETATE ION


Mass: 59.044 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C2H3O2
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 225 / 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: 2.43 Å3/Da / Density % sol: 49.32 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5.5
Details: 0.1 M MES, pH 5.5, 25% PEG4000, 0.15 M ammonium sulfate, VAPOR DIFFUSION, HANGING DROP, temperature 293K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL7-1 / Wavelength: 0.98 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Apr 29, 2011
RadiationMonochromator: side scattering I-beam bent single crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.98 Å / Relative weight: 1
ReflectionResolution: 1.75→50 Å / Num. all: 34913 / Num. obs: 34765 / % possible obs: 58.9 % / Observed criterion σ(F): 1 / Observed criterion σ(I): 1 / Redundancy: 6.5 % / Rmerge(I) obs: 0.048 / Rsym value: 0.04 / Net I/σ(I): 40.8
Reflection shellResolution: 1.75→1.78 Å / Redundancy: 6.6 % / Rmerge(I) obs: 0.781 / Mean I/σ(I) obs: 2 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
HKL-2000data collection
PHASERphasing
REFMAC5.5.0109refinement
HKL-2000data reduction
SCALEPACKdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 3LNJ

3lnj


Resolution: 1.8→20 Å / Cor.coef. Fo:Fc: 0.96 / Cor.coef. Fo:Fc free: 0.946 / SU B: 5.066 / SU ML: 0.092 / Cross valid method: THROUGHOUT / ESU R: 0.134 / ESU R Free: 0.126 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.23118 1585 5 %RANDOM
Rwork0.19769 ---
obs0.19942 30272 99.43 %-
all-30272 --
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 40.58 Å2
Baniso -1Baniso -2Baniso -3
1-0.39 Å20 Å20 Å2
2--0.06 Å20 Å2
3----0.45 Å2
Refinement stepCycle: LAST / Resolution: 1.8→20 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2398 0 36 225 2659
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.020.0222478
X-RAY DIFFRACTIONr_angle_refined_deg1.6852.0913301
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.835257
X-RAY DIFFRACTIONr_dihedral_angle_2_deg43.31923.11190
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.34315428
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.1681512
X-RAY DIFFRACTIONr_chiral_restr0.1240.2372
X-RAY DIFFRACTIONr_gen_planes_refined0.010.0211706
X-RAY DIFFRACTIONr_mcbond_it1.6881.51414
X-RAY DIFFRACTIONr_mcangle_it2.95322246
X-RAY DIFFRACTIONr_scbond_it5.07731064
X-RAY DIFFRACTIONr_scangle_it6.3324.51054
LS refinement shellResolution: 1.8→1.846 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.305 113 -
Rwork0.252 2172 -
obs--99.65 %
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)
10.8644-0.2780.64351.17420.08760.5798-0.09020.13090.06840.14260.0386-0.0733-0.02410.07620.05160.0574-0.0324-0.03150.14330.01140.081122.6911-47.13945.9224
20.42020.07030.27891.3255-0.53691.5794-0.0174-0.05440.0314-0.16080.1330.0702-0.1215-0.2413-0.11550.1219-0.001-0.07180.09550.04990.11269.6377-28.4365-3.2556
30.8253-0.180.10691.3871-0.06630.46970.07030.0195-0.03020.28220.0128-0.1816-0.02530.0106-0.08310.1283-0.0155-0.07110.0130.02430.127120.2131-9.2757.8303
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A26 - 109
2X-RAY DIFFRACTION2C26 - 108
3X-RAY DIFFRACTION3E25 - 108

+
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