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- PDB-2mps: Structure of complex of MDM2(3-109) and P73 TAD(10-25) -

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Basic information

Entry
Database: PDB / ID: 2mps
TitleStructure of complex of MDM2(3-109) and P73 TAD(10-25)
Components
  • E3 ubiquitin-protein ligase Mdm2
  • Tumor protein p73P73
KeywordsLIGASE/PEPTIDE / MDM2 / P73 TAD / P53 / LIGASE-PEPTIDE complex
Function / homology
Function and homology information


positive regulation of lung ciliated cell differentiation / negative regulation of cardiac muscle cell proliferation / 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 ...positive regulation of lung ciliated cell differentiation / negative regulation of cardiac muscle cell proliferation / 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 / TP53 Regulates Transcription of Death Receptors and Ligands / Activation of PUMA and translocation to mitochondria / ventricular septum development / endocardial cushion morphogenesis / Regulation of TP53 Activity through Association with Co-factors / positive regulation of oligodendrocyte differentiation / cellular response to alkaloid / positive regulation of muscle cell differentiation / SUMOylation of ubiquitinylation proteins / blood vessel development / TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain / regulation of protein catabolic process / TP53 Regulates Transcription of Caspase Activators and Caspases / cardiac septum morphogenesis / regulation of mitotic cell cycle / Constitutive Signaling by AKT1 E17K in Cancer / negative regulation of DNA damage response, signal transduction by p53 class mediator / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / response to magnesium ion / protein sumoylation / ligase activity / SUMOylation of transcription factors / protein localization to nucleus / cellular response to actinomycin D / negative regulation of neuron differentiation / mismatch repair / cellular response to UV-C / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / blood vessel remodeling / MDM2/MDM4 family protein binding / 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 / response to organonitrogen compound / 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 / transcription corepressor binding / response to cocaine / ubiquitin binding / kidney development / protein tetramerization / 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 / intrinsic apoptotic signaling pathway in response to DNA damage / 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 / cell junction / RUNX1 regulates transcription of genes involved in differentiation of HSCs / 5S rRNA binding / ubiquitin-dependent protein catabolic process / cellular response to hypoxia / proteasome-mediated ubiquitin-dependent protein catabolic process / regulation of gene expression / DNA-binding transcription activator activity, RNA polymerase II-specific / protein-containing complex assembly
Similarity search - Function
Tumour protein p73, SAM domain / 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 ...Tumour protein p73, SAM domain / 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 / 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 / SAM domain (Sterile alpha motif) / p53-like transcription factor, DNA-binding / Sterile alpha motif. / Sterile alpha motif domain / Sterile alpha motif/pointed domain superfamily / Zinc finger RING-type profile. / Zinc finger, RING-type / Zinc finger, RING/FYVE/PHD-type / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Tumor protein p73 / E3 ubiquitin-protein ligase Mdm2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodSOLUTION NMR / simulated annealing
Model detailsminimized average structure, model1
Model type detailsminimized average
AuthorsShin, J.S. / Ha, J.H. / Chi, S.W.
CitationJournal: Cell Cycle / Year: 2015
Title: Structural convergence of unstructured p53 family transactivation domains in MDM2 recognition
Authors: Shin, J.S. / Ha, J.H. / Lee, D.H. / Ryu, K.S. / Bae, K.H. / Park, B.C. / Park, S.G. / Yi, G.S. / Chi, S.W.
History
DepositionJun 2, 2014Deposition site: BMRB / Processing site: PDBJ
Revision 1.0Jun 3, 2015Provider: repository / Type: Initial release
Revision 1.1Jun 14, 2023Group: Data collection / Database references / Other
Category: database_2 / pdbx_database_status ...database_2 / pdbx_database_status / pdbx_nmr_software / 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_software.name / _pdbx_nmr_spectrometer.model

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: E3 ubiquitin-protein ligase Mdm2
B: Tumor protein p73


Theoretical massNumber of molelcules
Total (without water)14,0672
Polymers14,0672
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 / 100structures with the lowest energy
RepresentativeModel #1minimized average structure

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Components

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


Mass: 12275.253 Da / Num. of mol.: 1 / Fragment: UNP residues 3-109
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MDM2 / Production host: Escherichia coli (E. coli)
References: UniProt: Q00987, Ligases; Forming carbon-nitrogen bonds; Acid-amino-acid ligases (peptide synthases)
#2: Protein/peptide Tumor protein p73 / P73 / p53-like transcription factor / p53-related protein


Mass: 1791.846 Da / Num. of mol.: 1 / Fragment: UNP residues 10-25
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: P73, TP73 / Production host: Escherichia coli (E. coli) / References: UniProt: O15350

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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-13C HSQC aliphatic
1313D CBCA(CO)NH
1413D HNCO
1513D HN(CA)CB
1613D HBHA(CO)NH
1713D (H)CCH-TOCSY
1813D (H)CCH-COSY
1913D 1H-15N NOESY
11013D 1H-13C NOESY aliphatic
11113D 1H-13C NOESY aromatic

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Sample preparation

Details
Solution-IDContentsSolvent system
10.9 mM [U-99% 13C; U-99% 15N] E3 Ubiquitin-protein Ligase MDM2-1, 90% H2O/10% D2O90% H2O/10% D2O
20.9 mM [U-99% 13C; U-99% 15N] Tumor protein P73-2, 90% H2O/10% D2O90% H2O/10% D2O
Sample
Conc. (mg/ml)ComponentIsotopic labelingSolution-ID
0.9 mME3 Ubiquitin-protein Ligase MDM2-1[U-99% 13C; U-99% 15N]1
0.9 mMTumor protein P73-2[U-99% 13C; U-99% 15N]2
Sample conditionsIonic strength: 50 / pH: 6.5 / Pressure: ambient / Temperature: 283 K

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NMR measurement

NMR spectrometer
TypeManufacturerModelField strength (MHz)Spectrometer-ID
Bruker AvanceBrukerAVANCE8001
Bruker AvanceBrukerAVANCE9002

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Processing

NMR software
NameDeveloperClassification
X-PLOR_NIH_2.26SCHWIETERS, KUSZEWSKI, TJrefinement
CYANAGuntert, Mumenthaler and Wuthrichstructure solution
NMRDrawDelaglio, Grzesiek, Vuister, Zhu, Pfeifer and Baxprocessing
SparkyGoddardchemical shift assignment
TALOSCornilescu, Delaglio and Baxdata analysis
RefinementMethod: simulated annealing / Software ordinal: 1
NMR representativeSelection criteria: minimized average structure
NMR ensembleConformer selection criteria: structures with the lowest energy
Conformers calculated total number: 100 / Conformers submitted total number: 20 / Representative conformer: 1

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