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- PDB-2mwy: Mdmx-p53 -

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Basic information

Entry
Database: PDB / ID: 2mwy
TitleMdmx-p53
Components
  • Cellular tumor antigen p53P53
  • Protein Mdm4
KeywordsCell Cycle/Antitumor Protein / Cell Cycle-Antitumor Protein complex
Function / homology
Function and homology information


atrial septum development / heart valve development / Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / signal transduction by p53 class mediator / negative regulation of G1 to G0 transition / negative regulation of glucose catabolic process to lactate via pyruvate / Transcriptional activation of cell cycle inhibitor p21 / regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Activation of NOXA and translocation to mitochondria ...atrial septum development / heart valve development / Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / signal transduction by p53 class mediator / negative regulation of G1 to G0 transition / negative regulation of glucose catabolic process to lactate via pyruvate / Transcriptional activation of cell cycle inhibitor p21 / regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Activation of NOXA and translocation to mitochondria / negative regulation of pentose-phosphate shunt / ATP-dependent DNA/DNA annealing activity / negative regulation of helicase activity / regulation of cell cycle G2/M phase transition / intrinsic apoptotic signaling pathway in response to hypoxia / regulation of fibroblast apoptotic process / oxidative stress-induced premature senescence / oligodendrocyte apoptotic process / negative regulation of miRNA processing / positive regulation of thymocyte apoptotic process / glucose catabolic process to lactate via pyruvate / regulation of tissue remodeling / positive regulation of mitochondrial membrane permeability / negative regulation of mitophagy / positive regulation of programmed necrotic cell death / mRNA transcription / bone marrow development / circadian behavior / histone deacetylase regulator activity / RUNX3 regulates CDKN1A transcription / germ cell nucleus / regulation of mitochondrial membrane permeability involved in apoptotic process / atrioventricular valve morphogenesis / regulation of DNA damage response, signal transduction by p53 class mediator / TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain / TP53 Regulates Transcription of Death Receptors and Ligands / Activation of PUMA and translocation to mitochondria / ventricular septum development / DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / endocardial cushion morphogenesis / negative regulation of glial cell proliferation / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / negative regulation of neuroblast proliferation / Regulation of TP53 Activity through Association with Co-factors / mitochondrial DNA repair / T cell lineage commitment / positive regulation of execution phase of apoptosis / negative regulation of DNA replication / ER overload response / B cell lineage commitment / thymocyte apoptotic process / TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain / positive regulation of cardiac muscle cell apoptotic process / TP53 Regulates Transcription of Caspase Activators and Caspases / cardiac septum morphogenesis / entrainment of circadian clock by photoperiod / PI5P Regulates TP53 Acetylation / Association of TriC/CCT with target proteins during biosynthesis / Zygotic genome activation (ZGA) / necroptotic process / rRNA transcription / positive regulation of release of cytochrome c from mitochondria / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / TFIID-class transcription factor complex binding / mitophagy / SUMOylation of transcription factors / negative regulation of telomere maintenance via telomerase / general transcription initiation factor binding / intrinsic apoptotic signaling pathway by p53 class mediator / Transcriptional Regulation by VENTX / response to X-ray / DNA damage response, signal transduction by p53 class mediator / replicative senescence / chromosome organization / neuroblast proliferation / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / cellular response to UV-C / : / hematopoietic stem cell differentiation / negative regulation of reactive oxygen species metabolic process / T cell proliferation involved in immune response / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / glial cell proliferation / embryonic organ development / positive regulation of RNA polymerase II transcription preinitiation complex assembly / Pyroptosis / cis-regulatory region sequence-specific DNA binding / hematopoietic progenitor cell differentiation / cellular response to glucose starvation / cellular response to actinomycin D / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / somitogenesis / type II interferon-mediated signaling pathway / positive regulation of intrinsic apoptotic signaling pathway / negative regulation of stem cell proliferation / core promoter sequence-specific DNA binding / negative regulation of fibroblast proliferation / gastrulation / MDM2/MDM4 family protein binding / cardiac muscle cell apoptotic process
Similarity search - Function
MDM4 / MDM2 / SWIB/MDM2 domain / p53 negative regulator Mdm2/Mdm4 / SWIB/MDM2 domain / SWIB/MDM2 domain / SWIB/MDM2 domain profile. / SWIB/MDM2 domain superfamily / Cellular tumor antigen p53, transactivation domain 2 / Transactivation domain 2 ...MDM4 / MDM2 / SWIB/MDM2 domain / p53 negative regulator Mdm2/Mdm4 / SWIB/MDM2 domain / SWIB/MDM2 domain / SWIB/MDM2 domain profile. / SWIB/MDM2 domain superfamily / Cellular tumor antigen p53, transactivation domain 2 / Transactivation domain 2 / p53 transactivation domain / P53 transactivation motif / Zn-finger in Ran binding protein and others / p53 family signature. / p53, tetramerisation domain / P53 tetramerisation motif / p53, DNA-binding domain / P53 DNA-binding domain / p53 tumour suppressor family / p53-like tetramerisation domain superfamily / p53/RUNT-type transcription factor, DNA-binding domain superfamily / 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 / p53-like transcription factor, DNA-binding / Zinc finger RING-type profile. / Zinc finger, RING-type / Zinc finger, RING/FYVE/PHD-type / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Protein Mdm4 / Cellular tumor antigen p53
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodSOLUTION NMR
Model detailslowest energy, model1
AuthorsGrace, C.R.
CitationJournal: J.Mol.Biol. / Year: 2016
Title: Monitoring Ligand-Induced Protein Ordering in Drug Discovery.
Authors: Grace, C.R. / Ban, D. / Min, J. / Mayasundari, A. / Min, L. / Finch, K.E. / Griffiths, L. / Bharatham, N. / Bashford, D. / Kiplin Guy, R. / Dyer, M.A. / Kriwacki, R.W.
History
DepositionDec 3, 2014Deposition site: BMRB / Processing site: RCSB
Revision 1.0Jan 27, 2016Provider: repository / Type: Initial release
Revision 1.1Mar 16, 2016Group: Database references
Revision 1.2May 11, 2016Group: Database references
Revision 1.3Jun 14, 2023Group: Data collection / Database references / Other
Category: database_2 / pdbx_database_status / pdbx_nmr_spectrometer
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_nmr_data / _pdbx_nmr_spectrometer.model
Revision 1.4May 15, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2 / Item: _database_2.pdbx_DOI

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Protein Mdm4
B: Cellular tumor antigen p53


Theoretical massNumber of molelcules
Total (without water)11,9692
Polymers11,9692
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
NMR ensembles
DataCriteria
Number of conformers (submitted / calculated)20 / 100target function
RepresentativeModel #1lowest energy

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Components

#1: Protein Protein Mdm4 / Double minute 4 protein / Mdm2-like p53-binding protein / Protein Mdmx / p53-binding protein Mdm4


Mass: 10160.899 Da / Num. of mol.: 1 / Fragment: SWIB domain residues 23-111
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MDM4, MDMX / Production host: Escherichia coli (E. coli) / References: UniProt: O15151
#2: Protein/peptide Cellular tumor antigen p53 / P53 / Antigen NY-CO-13 / Phosphoprotein p53 / Tumor suppressor p53


Mass: 1807.973 Da / Num. of mol.: 1 / Fragment: residues 15-23 / Source method: obtained synthetically / Details: peptide synthesis / Source: (synth.) Homo sapiens (human) / References: UniProt: P04637

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Experimental details

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Experiment

ExperimentMethod: SOLUTION NMR
NMR experiment
Conditions-IDExperiment-IDSolution-IDType
1112D 1H-15N HSQC
1212D 1H-15N HSQC
1312D 1H-13C HSQC aliphatic
1412D 1H-13C HSQC aromatic
1513D HN(CA)CB
1613D CBCA(CO)NH
1713D HNCA
1813D (H)CCH-TOCSY
1913D H(CCO)NH
11013D 1H-13C NOESY aliphatic
11113D 1H-15N NOESY
11213D 1H-13C NOESY aromatic
11312D 1H-1H TOCSY
11412D 1H-1H NOESY

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Sample preparation

DetailsContents: 1.0 mM [U-100% 13C; U-100% 15N] protein 1, 1.2 mM protein 2, 90% H2O/10% D2O
Solvent system: 90% H2O/10% D2O
Sample
Conc. (mg/ml)ComponentIsotopic labelingSolution-ID
1.0 mMentity_1-1[U-100% 13C; U-100% 15N]1
1.2 mMentity_2-21
Sample conditionsIonic strength: 200 / pH: 7.0 / Pressure: ambient / Temperature: 298 K

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NMR measurement

NMR spectrometer
TypeManufacturerModelField strength (MHz)Spectrometer-ID
Bruker AvanceBrukerAVANCE6001
Bruker AvanceBrukerAVANCE8002

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Processing

NMR softwareName: CYANA / Developer: Guntert P. / Classification: refinement
NMR constraintsNOE constraints total: 1306 / NOE intraresidue total count: 391 / NOE long range total count: 334 / NOE medium range total count: 244 / NOE sequential total count: 337 / Hydrogen bond constraints total count: 20 / Protein phi angle constraints total count: 43 / Protein psi angle constraints total count: 43
NMR representativeSelection criteria: lowest energy
NMR ensembleConformer selection criteria: target function / Conformers calculated total number: 100 / Conformers submitted total number: 20

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