+Open data
-Basic information
Entry | Database: PDB / ID: 4ogn | ||||||
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Title | Co-Crystal Structure of MDM2 with Inhbitor Compound 3 | ||||||
Components | E3 ubiquitin-protein ligase Mdm2 | ||||||
Keywords | LIGASE/LIGASE INHIBITOR / P53 / PROTEIN-PROTEIN INTERACTION / LIGASE-LIGASE 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 / negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator / response to ether / 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 / negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator / response to ether / 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 / response to iron ion / negative regulation of protein processing / response to steroid hormone / NEDD8 ligase activity / AKT phosphorylates targets in the cytosol / atrioventricular valve morphogenesis / cellular response to peptide hormone stimulus / ventricular septum development / endocardial cushion morphogenesis / positive regulation of muscle cell differentiation / SUMOylation of ubiquitinylation proteins / cellular response to alkaloid / blood vessel development / regulation of protein catabolic process / cardiac septum morphogenesis / Constitutive Signaling by AKT1 E17K in Cancer / ligase activity / negative regulation of DNA damage response, signal transduction by p53 class mediator / response to magnesium ion / SUMOylation of transcription factors / 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 / NPAS4 regulates expression of target genes / transcription repressor complex / regulation of heart rate / positive regulation of mitotic cell cycle / positive regulation of protein export from nucleus / response to cocaine / proteolysis involved in protein catabolic process / ubiquitin binding / Stabilization of p53 / Regulation of RUNX3 expression and activity / protein destabilization / RING-type E3 ubiquitin transferase / establishment of protein localization / Oncogene Induced Senescence / Signaling by ALK fusions and activated point mutants / Regulation of TP53 Activity through Methylation / cellular response to gamma radiation / response to toxic substance / cellular response to growth factor stimulus / cellular response to hydrogen peroxide / protein polyubiquitination / ubiquitin-protein transferase activity / endocytic vesicle membrane / ubiquitin protein ligase activity / disordered domain specific binding / Regulation of TP53 Degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / p53 binding / negative regulation of neuron projection development / 5S rRNA binding / cellular response to hypoxia / ubiquitin-dependent protein catabolic process / regulation of gene expression / protein-containing complex assembly / proteasome-mediated ubiquitin-dependent protein catabolic process / Oxidative Stress Induced Senescence / Regulation of TP53 Activity through Phosphorylation / amyloid fibril formation / Ub-specific processing proteases / regulation of cell cycle / protein ubiquitination / 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 / enzyme binding / negative regulation of transcription by RNA polymerase II / protein-containing complex / zinc ion binding / nucleoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.377 Å | ||||||
Authors | Shaffer, P.L. / Huang, X. / Yakowec, P. / Long, A.M. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2014 Title: Novel Inhibitors of the MDM2-p53 Interaction Featuring Hydrogen Bond Acceptors as Carboxylic Acid Isosteres. Authors: Gonzalez, A.Z. / Li, Z. / Beck, H.P. / Canon, J. / Chen, A. / Chow, D. / Duquette, J. / Eksterowicz, J. / Fox, B.M. / Fu, J. / Huang, X. / Houze, J. / Jin, L. / Li, Y. / Ling, Y. / Lo, M.C. ...Authors: Gonzalez, A.Z. / Li, Z. / Beck, H.P. / Canon, J. / Chen, A. / Chow, D. / Duquette, J. / Eksterowicz, J. / Fox, B.M. / Fu, J. / Huang, X. / Houze, J. / Jin, L. / Li, Y. / Ling, Y. / Lo, M.C. / Long, A.M. / McGee, L.R. / McIntosh, J. / Oliner, J.D. / Osgood, T. / Rew, Y. / Saiki, A.Y. / Shaffer, P. / Wortman, S. / Yakowec, P. / Yan, X. / Ye, Q. / Yu, D. / Zhao, X. / Zhou, J. / Olson, S.H. / Sun, D. / Medina, J.C. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4ogn.cif.gz | 59.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4ogn.ent.gz | 42.3 KB | Display | PDB format |
PDBx/mmJSON format | 4ogn.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4ogn_validation.pdf.gz | 809.6 KB | Display | wwPDB validaton report |
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Full document | 4ogn_full_validation.pdf.gz | 811.7 KB | Display | |
Data in XML | 4ogn_validation.xml.gz | 8.8 KB | Display | |
Data in CIF | 4ogn_validation.cif.gz | 11.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/og/4ogn ftp://data.pdbj.org/pub/pdb/validation_reports/og/4ogn | HTTPS FTP |
-Related structure data
Related structure data | 4occC 4odeC 4odfC 4ogtC 4ogvC 4erfS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 12045.075 Da / Num. of mol.: 1 / Fragment: UNP Residues 6-110 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) | ||
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#2: Chemical | ChemComp-2U5 / | ||
#3: Chemical | #4: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.59 Å3/Da / Density % sol: 52.5 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 5 Details: 0.8-1.8M Ammonium Sulfate, 0.1M sodium citrate, pH 5.0, VAPOR DIFFUSION, HANGING DROP, temperature 277K |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: RAYONIX MX-300 / Detector: CCD / Date: Nov 20, 2012 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.377→50 Å / Num. obs: 25881 / % possible obs: 99.8 % / Redundancy: 13.1 % / Rmerge(I) obs: 0.097 / Χ2: 1.057 / Net I/σ(I): 7.2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB Entry 4ERF Resolution: 1.377→38.734 Å / Occupancy max: 1 / Occupancy min: 0.44 / SU ML: 0.12 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 56.86 Å2 / Biso mean: 20.6255 Å2 / Biso min: 10.07 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.377→38.734 Å
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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