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Yorodumi- PDB-5c84: Fragment-Based Drug Discovery Targeting Inhibitor of Apoptosis Pr... -
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-Basic information
Entry | Database: PDB / ID: 5c84 | ||||||
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Title | Fragment-Based Drug Discovery Targeting Inhibitor of Apoptosis Proteins: Compound 20 | ||||||
Components | E3 ubiquitin-protein ligase XIAP | ||||||
Keywords | APOPTOSIS / ligase | ||||||
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 / MOLECULAR REPLACEMENT / Resolution: 2.36 Å | ||||||
Authors | Chessari, G. / Buck, I.M. / Day, J.E.H. / Day, P.J. / Iqbal, A. / Johnson, C.N. / Lewis, E.J. / Martins, V. / Miller, D. / Reader, M. ...Chessari, G. / Buck, I.M. / Day, J.E.H. / Day, P.J. / Iqbal, A. / Johnson, C.N. / Lewis, E.J. / Martins, V. / Miller, D. / Reader, M. / Rees, D.C. / Rich, S.J. / Tamanini, E. / Vitorino, M. / Ward, G.A. / Williams, P.A. / Williams, G. / Wilsher, N.E. / Woolford, A.J.-A. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2015 Title: Fragment-Based Drug Discovery Targeting Inhibitor of Apoptosis Proteins: Discovery of a Non-Alanine Lead Series with Dual Activity Against cIAP1 and XIAP. Authors: Chessari, G. / Buck, I.M. / Day, J.E. / Day, P.J. / Iqbal, A. / Johnson, C.N. / Lewis, E.J. / Martins, V. / Miller, D. / Reader, M. / Rees, D.C. / Rich, S.J. / Tamanini, E. / Vitorino, M. / ...Authors: Chessari, G. / Buck, I.M. / Day, J.E. / Day, P.J. / Iqbal, A. / Johnson, C.N. / Lewis, E.J. / Martins, V. / Miller, D. / Reader, M. / Rees, D.C. / Rich, S.J. / Tamanini, E. / Vitorino, M. / Ward, G.A. / Williams, P.A. / Williams, G. / Wilsher, N.E. / Woolford, A.J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5c84.cif.gz | 65.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5c84.ent.gz | 47 KB | Display | PDB format |
PDBx/mmJSON format | 5c84.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5c84_validation.pdf.gz | 799.7 KB | Display | wwPDB validaton report |
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Full document | 5c84_full_validation.pdf.gz | 800.2 KB | Display | |
Data in XML | 5c84_validation.xml.gz | 8.5 KB | Display | |
Data in CIF | 5c84_validation.cif.gz | 11.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/c8/5c84 ftp://data.pdbj.org/pub/pdb/validation_reports/c8/5c84 | HTTPS FTP |
-Related structure data
Related structure data | 5c0kC 5c0lC 5c3hC 5c3kC 5c7aC 5c7bC 5c7cC 5c7dC 5c83C 2opyS C: citing same article (ref.) S: Starting model for refinement |
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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 on special symmetry positions |
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-Components
#1: Protein | Mass: 12686.206 Da / Num. of mol.: 1 / Fragment: UNP residues 249-354 Source method: isolated from a genetically manipulated source Details: Image clone / Source: (gene. exp.) Homo sapiens (human) / Gene: XIAP, API3, BIRC4, IAP3 / Plasmid: pET 28b / Production host: Escherichia coli BL21(DE3) (bacteria) References: UniProt: P98170, Ligases; Forming carbon-nitrogen bonds; Acid-amino-acid ligases (peptide synthases) |
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#2: Chemical | ChemComp-ZN / |
#3: Chemical | ChemComp-4YL / ( |
#4: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION |
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-Sample preparation
Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7.5 / Details: 0.1M Hepes-NaOH 7.5, 3.9M NaCl / PH range: 7.5 |
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-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU FR-E+ SUPERBRIGHT / Wavelength: 1.54 Å |
Detector | Type: RIGAKU SATURN A200 / Detector: CCD / Date: Nov 18, 2010 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54 Å / Relative weight: 1 |
Reflection | Resolution: 2.34→50.2 Å / Num. obs: 11645 / % possible obs: 97 % / Redundancy: 2.4 % / Rmerge(I) obs: 0.035 / Net I/σ(I): 4.8 |
Reflection shell | Resolution: 2.34→2.43 Å / Rmerge(I) obs: 0.125 / Mean I/σ(I) obs: 5.5 / % possible all: 96.2 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2OPY Resolution: 2.36→50.2 Å / Cor.coef. Fo:Fc: 0.94 / Cor.coef. Fo:Fc free: 0.895 / SU B: 8.643 / SU ML: 0.123 / Cross valid method: THROUGHOUT / ESU R: 0.197 / ESU R Free: 0.2 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT
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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: BABINET MODEL WITH MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 41.079 Å2
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Refinement step | Cycle: 1 / Resolution: 2.36→50.2 Å
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Refine LS restraints |
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