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Yorodumi- PDB-4kju: Crystal structure of XIAP-Bir2 with a bound benzodiazepinone inhi... -
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-Basic information
Entry | Database: PDB / ID: 4kju | ||||||
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Title | Crystal structure of XIAP-Bir2 with a bound benzodiazepinone inhibitor. | ||||||
Components | E3 ubiquitin-protein ligase XIAP | ||||||
Keywords | APOPTOSIS/APOPTOSIS INHIBITOR / XIAP inhibitors / BIR2 / benzodiazepinone / oncology / caspase / APOPTOSIS-APOPTOSIS INHIBITOR complex | ||||||
Function / homology | Function and homology information endopeptidase regulator activity / inhibition of cysteine-type endopeptidase activity / regulation of apoptosis involved in tissue homeostasis / positive regulation of protein linear polyubiquitination / regulation of BMP signaling pathway / copper ion homeostasis / nucleotide-binding oligomerization domain containing 1 signaling pathway / regulation of nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / nucleotide-binding oligomerization domain containing 2 signaling pathway / SMAC, XIAP-regulated apoptotic response ...endopeptidase regulator activity / inhibition of cysteine-type endopeptidase activity / regulation of apoptosis involved in tissue homeostasis / positive regulation of protein linear polyubiquitination / regulation of BMP signaling pathway / copper ion homeostasis / nucleotide-binding oligomerization domain containing 1 signaling pathway / regulation of nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / nucleotide-binding oligomerization domain containing 2 signaling pathway / SMAC, XIAP-regulated apoptotic response / Activation of caspases through apoptosome-mediated cleavage / Regulation of the apoptosome activity / SMAC (DIABLO) binds to IAPs / SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes / TNFR1-induced proapoptotic signaling / RIPK1-mediated regulated necrosis / cysteine-type endopeptidase inhibitor activity / regulation of innate immune response / positive regulation of type I interferon production / protein K63-linked ubiquitination / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / negative regulation of tumor necrosis factor-mediated signaling pathway / protein serine/threonine kinase binding / Regulation of PTEN localization / : / positive regulation of protein ubiquitination / TNFR1-induced NF-kappa-B signaling pathway / Deactivation of the beta-catenin transactivating complex / Regulation of TNFR1 signaling / positive regulation of JNK cascade / RING-type E3 ubiquitin transferase / Regulation of necroptotic cell death / Wnt signaling pathway / Regulation of PTEN stability and activity / ubiquitin-protein transferase activity / ubiquitin protein ligase activity / positive regulation of canonical Wnt signaling pathway / regulation of cell population proliferation / regulation of inflammatory response / regulation of apoptotic process / positive regulation of canonical NF-kappaB signal transduction / neuron apoptotic process / regulation of cell cycle / defense response to bacterium / DNA damage response / negative regulation of apoptotic process / nucleoplasm / identical protein binding / nucleus / metal ion binding / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 1.6 Å | ||||||
Authors | Lukacs, C.M. / Janson, C.A. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2013 Title: Optimization of Benzodiazepinones as Selective Inhibitors of the X-Linked Inhibitor of Apoptosis Protein (XIAP) Second Baculovirus IAP Repeat (BIR2) Domain. Authors: Kester, R.F. / Donnell, A.F. / Lou, Y. / Remiszewski, S.W. / Lombardo, L.J. / Chen, S. / Le, N.T. / Lo, J. / Moliterni, J.A. / Han, X. / Hogg, J.H. / Liang, W. / Michoud, C. / Rupert, K.C. / ...Authors: Kester, R.F. / Donnell, A.F. / Lou, Y. / Remiszewski, S.W. / Lombardo, L.J. / Chen, S. / Le, N.T. / Lo, J. / Moliterni, J.A. / Han, X. / Hogg, J.H. / Liang, W. / Michoud, C. / Rupert, K.C. / Mischke, S. / Le, K. / Weisel, M. / Janson, C.A. / Lukacs, C.M. / Fretland, A.J. / Hong, K. / Polonskaia, A. / Gao, L. / Li, S. / Solis, D.S. / Aguilar, D. / Tardell, C. / Dvorozniak, M. / Tannu, S. / Lee, E.C. / Schutt, A.D. / Goggin, B. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4kju.cif.gz | 50.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4kju.ent.gz | 35.4 KB | Display | PDB format |
PDBx/mmJSON format | 4kju.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4kju_validation.pdf.gz | 785.3 KB | Display | wwPDB validaton report |
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Full document | 4kju_full_validation.pdf.gz | 787.6 KB | Display | |
Data in XML | 4kju_validation.xml.gz | 10.1 KB | Display | |
Data in CIF | 4kju_validation.cif.gz | 13.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kj/4kju ftp://data.pdbj.org/pub/pdb/validation_reports/kj/4kju | HTTPS FTP |
-Related structure data
Related structure data | 4kjvC 4j3yS 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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2 |
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Unit cell |
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Details | monomer |
-Components
#1: Protein | Mass: 9936.131 Da / Num. of mol.: 2 / Fragment: XIAP-Bir2 (unp residues 152-236) / Mutation: C202A, C213G Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: XIAP, API3, BIRC4, IAP3 / Plasmid: pET28A / Production host: Escherichia coli (E. coli) / Strain (production host): Rosetta2(DE3)PLysS References: UniProt: P98170, Ligases; Forming carbon-nitrogen bonds; Acid-amino-acid ligases (peptide synthases) #2: Chemical | #3: Chemical | ChemComp-1RH / | #4: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 1.96 Å3/Da / Density % sol: 37.39 % |
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Crystal grow | Temperature: 292 K / Method: vapor diffusion, sitting drop / pH: 7 Details: 1.5 M ammonium sulfate, 125 mM Bis-tris-propane , pH 7.0, VAPOR DIFFUSION, SITTING DROP, temperature 292K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 0.99987 Å |
Detector | Type: PSI PILATUS 6M / Detector: PIXEL / Date: Mar 30, 2012 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.99987 Å / Relative weight: 1 |
Reflection | Resolution: 1.6→38.2 Å / Num. obs: 21271 / % possible obs: 99.9 % / Redundancy: 12.4 % / Biso Wilson estimate: 21.64 Å2 / Rsym value: 0.058 / Net I/σ(I): 22.9 |
Reflection shell | Resolution: 1.6→1.69 Å / Redundancy: 13 % / Rmerge(I) obs: 0.423 / Mean I/σ(I) obs: 5.7 / Num. unique all: 3045 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: 4J3Y Resolution: 1.6→38.2 Å / Cor.coef. Fo:Fc: 0.966 / Cor.coef. Fo:Fc free: 0.953 / SU B: 1.866 / SU ML: 0.065 / Cross valid method: THROUGHOUT / ESU R: 0.092 / ESU R Free: 0.093 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 26.276 Å2
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Refinement step | Cycle: LAST / Resolution: 1.6→38.2 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.6→1.641 Å / Total num. of bins used: 20
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