+Open data
-Basic information
Entry | Database: PDB / ID: 4odf | ||||||
---|---|---|---|---|---|---|---|
Title | Co-Crystal Structure of MDM2 with Inhibitor Compound 47 | ||||||
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 / negative regulation of protein processing / response to steroid hormone / NEDD8 ligase activity / response to iron ion / AKT phosphorylates targets in the cytosol / cellular response to peptide hormone stimulus / atrioventricular valve morphogenesis / ventricular septum development / endocardial cushion morphogenesis / positive regulation of muscle cell differentiation / SUMOylation of ubiquitinylation proteins / cellular response to alkaloid / 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 / 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 / proteolysis involved in protein catabolic process / response to cocaine / 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 / Regulation of TP53 Activity through Methylation / p53 binding / response to toxic substance / cellular response to gamma radiation / cellular response to growth factor stimulus / cellular response to hydrogen peroxide / Regulation of TP53 Degradation / protein polyubiquitination / ubiquitin-protein transferase activity / disordered domain specific binding / endocytic vesicle membrane / ubiquitin protein ligase activity / Signaling by ALK fusions and activated point mutants / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / negative regulation of neuron projection development / cellular response to hypoxia / regulation of gene expression / 5S rRNA binding / ubiquitin-dependent protein catabolic process / protein-containing complex assembly / Regulation of TP53 Activity through Phosphorylation / Oxidative Stress Induced Senescence / proteasome-mediated ubiquitin-dependent protein catabolic process / 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 / positive regulation of cell population proliferation / ubiquitin protein ligase binding / positive regulation of gene expression / negative regulation of apoptotic process / nucleolus / 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: 2.2006 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 |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 4odf.cif.gz | 56.3 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb4odf.ent.gz | 40 KB | Display | PDB format |
PDBx/mmJSON format | 4odf.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/od/4odf ftp://data.pdbj.org/pub/pdb/validation_reports/od/4odf | HTTPS FTP |
---|
-Related structure data
Related structure data | 4occC 4odeC 4ognC 4ogtC 4ogvC 4erfS S: Starting model for refinement C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-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) |
---|---|
#2: Chemical | ChemComp-2U1 / |
#3: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.45 Å3/Da / Density % sol: 49.72 % |
---|---|
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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Oct 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: 2.2→50 Å / Num. obs: 6540 / % possible obs: 93.2 % / Redundancy: 7 % / Rmerge(I) obs: 0.18 / Χ2: 1.852 / Net I/σ(I): 4.8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
|
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB Entry 4ERF Resolution: 2.2006→34.814 Å / Occupancy max: 1 / Occupancy min: 0 / FOM work R set: 0.6773 / SU ML: 0.28 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 34.97 / Stereochemistry target values: ML
| ||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 89.46 Å2 / Biso mean: 36.9346 Å2 / Biso min: 15.95 Å2 | ||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.2006→34.814 Å
| ||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 2
| ||||||||||||||||||||||||||||||||||||||||
Refinement TLS params. | Method: refined / Origin x: 13.127 Å / Origin y: -17.0897 Å / Origin z: -6.297 Å
| ||||||||||||||||||||||||||||||||||||||||
Refinement TLS group | Selection details: chain 'A' and (resid 12 through 110 ) |