+Open data
-Basic information
Entry | Database: PDB / ID: 5m6h | ||||||
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Title | Small Molecule inhibitors of IAP | ||||||
Components | E3 ubiquitin-protein ligase XIAP | ||||||
Keywords | LIGASE / XIAP / Apoptosis / metal-binding / inhibitor | ||||||
Function / homology | Function and homology information endopeptidase regulator activity / regulation of apoptosis involved in tissue homeostasis / inhibition of cysteine-type endopeptidase activity / 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 / protein serine/threonine kinase binding / nucleotide-binding oligomerization domain containing 2 signaling pathway ...endopeptidase regulator activity / regulation of apoptosis involved in tissue homeostasis / inhibition of cysteine-type endopeptidase activity / 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 / protein serine/threonine kinase binding / nucleotide-binding oligomerization domain containing 2 signaling pathway / SMAC, XIAP-regulated apoptotic response / Regulation of the apoptosome activity / Activation of caspases through apoptosome-mediated cleavage / SMAC (DIABLO) binds to IAPs / SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes / TNFR1-induced proapoptotic signaling / regulation of innate immune response / RIPK1-mediated regulated necrosis / cysteine-type endopeptidase inhibitor activity / protein K63-linked ubiquitination / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / positive regulation of type I interferon production / negative regulation of tumor necrosis factor-mediated signaling pathway / Regulation of PTEN localization / TNFR1-induced NF-kappa-B signaling pathway / positive regulation of protein ubiquitination / Deactivation of the beta-catenin transactivating complex / Regulation of TNFR1 signaling / positive regulation of JNK cascade / RING-type E3 ubiquitin transferase / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / Regulation of necroptotic cell death / Wnt signaling pathway / Regulation of PTEN stability and activity / ubiquitin-protein transferase activity / positive regulation of canonical Wnt signaling pathway / ubiquitin protein ligase activity / regulation of cell population proliferation / regulation of inflammatory response / neuron apoptotic process / regulation of apoptotic process / positive regulation of canonical NF-kappaB signal transduction / regulation of cell cycle / defense response to bacterium / DNA damage response / negative regulation of apoptotic process / nucleoplasm / identical protein binding / metal ion binding / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / FOURIER SYNTHESIS / Resolution: 2.5 Å | ||||||
Authors | Williams, P.A. | ||||||
Citation | Journal: J. Med. Chem. / Year: 2017 Title: Discovery of a Potent Nonpeptidomimetic, Small-Molecule Antagonist of Cellular Inhibitor of Apoptosis Protein 1 (cIAP1) and X-Linked Inhibitor of Apoptosis Protein (XIAP). Authors: Tamanini, E. / Buck, I.M. / Chessari, G. / Chiarparin, E. / Day, J.E.H. / Frederickson, M. / Griffiths-Jones, C.M. / Hearn, K. / Heightman, T.D. / Iqbal, A. / Johnson, C.N. / Lewis, E.J. / ...Authors: Tamanini, E. / Buck, I.M. / Chessari, G. / Chiarparin, E. / Day, J.E.H. / Frederickson, M. / Griffiths-Jones, C.M. / Hearn, K. / Heightman, T.D. / Iqbal, A. / Johnson, C.N. / Lewis, E.J. / Martins, V. / Peakman, T. / Reader, M. / Rich, S.J. / Ward, G.A. / Williams, P.A. / Wilsher, N.E. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5m6h.cif.gz | 62.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5m6h.ent.gz | 48.2 KB | Display | PDB format |
PDBx/mmJSON format | 5m6h.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/m6/5m6h ftp://data.pdbj.org/pub/pdb/validation_reports/m6/5m6h | HTTPS FTP |
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-Related 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: 14575.300 Da / Num. of mol.: 1 Mutation: Deletion 1-248,deletion 355-497, insertion 240 MGSSHHHHHHSSGLVPRGSH Source method: isolated from a genetically manipulated source 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-NA / |
#4: Chemical | ChemComp-7J6 / |
#5: 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: 4.57 Å3/Da / Density % sol: 73.06 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 8 / Details: 0.1M HEPES/NaOH pH8, 3.3M NaCl |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU FR-E SUPERBRIGHT / Wavelength: 1.54187 Å |
Detector | Type: RIGAKU SATURN 944+ / Detector: CCD / Date: Jun 8, 2011 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54187 Å / Relative weight: 1 |
Reflection | Resolution: 2.478→70.99 Å / Num. obs: 9900 / % possible obs: 97.8 % / Redundancy: 2.4 % / Biso Wilson estimate: 53.21 Å2 / Rmerge(I) obs: 0.071 / Net I/σ(I): 11.1 |
Reflection shell | Resolution: 2.48→2.61 Å / Rmerge(I) obs: 0.478 / Mean I/σ(I) obs: 2 / % possible all: 96.7 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS / Resolution: 2.5→35.49 Å / Cor.coef. Fo:Fc: 0.939 / Cor.coef. Fo:Fc free: 0.881 / Rfactor Rfree error: 0.01 / SU R Cruickshank DPI: 0.21 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.258 / SU Rfree Blow DPI: 0.245 / SU Rfree Cruickshank DPI: 0.221
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Displacement parameters | Biso mean: 42.711 Å2
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Refine analyze | Luzzati coordinate error obs: 0.28 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Resolution: 2.5→35.49 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.5→2.79 Å / Rfactor Rfree error: 0 / Total num. of bins used: 5
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Refinement TLS params. | Method: refined / Origin x: -16.9891 Å / Origin y: -29.1181 Å / Origin z: -4.3605 Å
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Refinement TLS group | Selection details: { A|248 - A|351 } |