[English] 日本語
Yorodumi- PDB-4j7e: The 1.63A crystal structure of humanized Xenopus MDM2 with a nutl... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4j7e | ||||||
---|---|---|---|---|---|---|---|
Title | The 1.63A crystal structure of humanized Xenopus MDM2 with a nutlin fragment, RO5524529 | ||||||
Components | E3 ubiquitin-protein ligase Mdm2 | ||||||
Keywords | LIGASE/ANTAGONIST / PROTEIN-PROTEIN INTERACTION / LIGASE-ANTAGONIST COMPLEX / MDM2 / E3 UBIQUITIN LIGASE / P53 / IMIDAZOLINE / NUCLEUS | ||||||
Function / homology | Function and homology information regulation of biological quality / RING-type E3 ubiquitin transferase / ubiquitin protein ligase activity / p53 binding / regulation of gene expression / regulation of cell cycle / protein ubiquitination / negative regulation of apoptotic process / nucleolus / apoptotic process ...regulation of biological quality / RING-type E3 ubiquitin transferase / ubiquitin protein ligase activity / p53 binding / regulation of gene expression / regulation of cell cycle / protein ubiquitination / negative regulation of apoptotic process / nucleolus / apoptotic process / nucleoplasm / identical protein binding / nucleus / metal ion binding / cytoplasm Similarity search - Function | ||||||
Biological species | Xenopus laevis (African clawed frog) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.63 Å | ||||||
Authors | Janson, C. / Lukacs, C. / Graves, B. | ||||||
Citation | Journal: ACS Med Chem Lett / Year: 2013 Title: Deconstruction of a nutlin: dissecting the binding determinants of a potent protein-protein interaction inhibitor. Authors: Fry, D.C. / Wartchow, C. / Graves, B. / Janson, C. / Lukacs, C. / Kammlott, U. / Belunis, C. / Palme, S. / Klein, C. / Vu, B. #1: Journal: To be Published Title: MDM2 small-molecule antagonist RG7112 activates P53 signaling and regresses human tumors in preclinical cancer models Authors: Tovar, C. / Graves, B. / Packman, K. / Filipovic, Z. / Higgins, B. / Xia, M. / Tardell, C. / Garrido, R. / Lee, E. / Kolinsky, K. / To, K.-H. / Linn, M. / Podlaski, F. / Wovkulich, P. / Vu, B. / Vassilev, L.T. #2: Journal: To be Published Title: Discovery of RG7112: a small-molecule MDM2 antagonist in clinical development Authors: Vu, B. / Wovkulich, P. / Pizzolato, G. / Lovey, A. / Ding, Q. / Jiang, N. / Liu, J.-J. / Zhao, C. / Glenn, K. / Wen, Y. / Tovar, C. / Thompson, T. / Packman, K. / Vassilev, L. / Graves, B. #3: Journal: Science / Year: 2004 Title: In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Authors: Vassilev, L.T. / Vu, B.T. / Graves, B. / Carvajal, D. / Podlaski, F. / Filipovic, Z. / Kong, N. / Kammlott, U. / Lukacs, C. / Klein, C. / Fotouhi, N. / Liu, E.A. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 4j7e.cif.gz | 33.8 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb4j7e.ent.gz | 21.8 KB | Display | PDB format |
PDBx/mmJSON format | 4j7e.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4j7e_validation.pdf.gz | 721.2 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 4j7e_full_validation.pdf.gz | 722.5 KB | Display | |
Data in XML | 4j7e_validation.xml.gz | 7 KB | Display | |
Data in CIF | 4j7e_validation.cif.gz | 8.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/j7/4j7e ftp://data.pdbj.org/pub/pdb/validation_reports/j7/4j7e | HTTPS FTP |
-Related structure data
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
| ||||||||
Details | N-TERMINAL FRAGMENT EXISTS AS A MONOMER BUT FULL-LENGTH PROTEIN FORMS A DIMER |
-Components
#1: Protein | Mass: 9962.615 Da / Num. of mol.: 1 / Fragment: N-terminal domain (UNP residues 21-105) / Mutation: I50L, P92H, L95I Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Gene: mdm2 / Plasmid: PUBS 520 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 References: UniProt: P56273, Ligases; Forming carbon-nitrogen bonds; Acid-amino-acid ligases (peptide synthases) |
---|---|
#2: Chemical | ChemComp-I29 / [( |
#3: Chemical | ChemComp-SO4 / |
#4: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.51 Å3/Da / Density % sol: 50.99 % |
---|---|
Crystal grow | Temperature: 278 K / Method: vapor diffusion, hanging drop / pH: 6.5 Details: 40-50% SATURATED AMMONIUM SULFATE, 0.1m MES, PH 6.5, 5% PEG200, VAPOR DIFFUSION, HANGING DROP, temperature 278K |
-Data collection
Diffraction | Mean temperature: 80 K |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1 Å |
Detector | Type: PSI PILATUS 6M / Detector: PIXEL / Date: Sep 22, 2012 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.46→37 Å / Num. all: 17553 / Num. obs: 16986 / % possible obs: 98.5 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 6.2 % / Biso Wilson estimate: 22.5 Å2 / Rmerge(I) obs: 0.061 / Net I/σ(I): 7.9 |
Reflection shell | Resolution: 1.46→1.54 Å / Redundancy: 5.2 % / Rmerge(I) obs: 0.998 / Mean I/σ(I) obs: 0.9 / Num. unique all: 2305 / % possible all: 98.5 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.63→34.31 Å / Rfactor Rfree error: 0.009 / Data cutoff high absF: 1370215.6 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0
| ||||||||||||||||||||||||||||||||||||
Solvent computation | Solvent model: FLAT MODEL / Bsol: 50.2498 Å2 / ksol: 0.39486 e/Å3 | ||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 25.1 Å2
| ||||||||||||||||||||||||||||||||||||
Refine analyze |
| ||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.63→34.31 Å
| ||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||
Refine LS restraints NCS | NCS model details: NONE | ||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 1.63→1.73 Å / Rfactor Rfree error: 0.027 / Total num. of bins used: 6
| ||||||||||||||||||||||||||||||||||||
Xplor file |
|