+Open data
-Basic information
Entry | Database: PDB / ID: 6h6q | ||||||
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Title | Fragment Derived XIAP inhibitor | ||||||
Components | E3 ubiquitin-protein ligase XIAP | ||||||
Keywords | APOPTOSIS / inhibitor of apoptosis / caspase inhibitor zinc binding domain | ||||||
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: 2.63 Å | ||||||
Authors | Williams, P.A. | ||||||
Citation | Journal: J. Med. Chem. / Year: 2018 Title: A Fragment-Derived Clinical Candidate for Antagonism of X-Linked and Cellular Inhibitor of Apoptosis Proteins: 1-(6-[(4-Fluorophenyl)methyl]-5-(hydroxymethyl)-3,3-dimethyl-1 H,2 H,3 H- ...Title: A Fragment-Derived Clinical Candidate for Antagonism of X-Linked and Cellular Inhibitor of Apoptosis Proteins: 1-(6-[(4-Fluorophenyl)methyl]-5-(hydroxymethyl)-3,3-dimethyl-1 H,2 H,3 H-pyrrolo[3,2- b]pyridin-1-yl)-2-[(2 R,5 R)-5-methyl-2-([(3R)-3-methylmorpholin-4-yl]methyl)piperazin-1-yl]ethan-1-one (ASTX660). Authors: Johnson, C.N. / Ahn, J.S. / Buck, I.M. / Chiarparin, E. / Day, J.E.H. / Hopkins, A. / Howard, S. / Lewis, E.J. / Martins, V. / Millemaggi, A. / Munck, J.M. / Page, L.W. / Peakman, T. / ...Authors: Johnson, C.N. / Ahn, J.S. / Buck, I.M. / Chiarparin, E. / Day, J.E.H. / Hopkins, A. / Howard, S. / Lewis, E.J. / Martins, V. / Millemaggi, A. / Munck, J.M. / Page, L.W. / Peakman, T. / Reader, M. / Rich, S.J. / Saxty, G. / Smyth, T. / Thompson, N.T. / Ward, G.A. / Williams, P.A. / Wilsher, N.E. / Chessari, G. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6h6q.cif.gz | 107.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6h6q.ent.gz | 87.3 KB | Display | PDB format |
PDBx/mmJSON format | 6h6q.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/h6/6h6q ftp://data.pdbj.org/pub/pdb/validation_reports/h6/6h6q | 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
#1: Protein | Mass: 14575.300 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Details: Protein domain / Source: (gene. exp.) Homo sapiens (human) / Gene: XIAP, API3, BIRC4, IAP3 / Production host: Escherichia coli BL21(DE3) (bacteria) References: UniProt: P98170, RING-type E3 ubiquitin transferase #2: Chemical | #3: Chemical | #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: 4.54 Å3/Da / Density % sol: 72.93 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8 / Details: 3M NaCl .1M pH=8 HEPES/NaOH |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU FR-X / Wavelength: 1.54187 Å |
Detector | Type: RIGAKU SATURN 944 / Detector: CCD / Date: Nov 9, 2012 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54187 Å / Relative weight: 1 |
Reflection | Resolution: 2.63→72.874 Å / Num. obs: 16462 / % possible obs: 97.8 % / Redundancy: 2.4 % / Biso Wilson estimate: 64.53 Å2 / Rrim(I) all: 0.098 / Net I/σ(I): 8.3 |
Reflection shell | Resolution: 2.63→2.68 Å / Mean I/σ(I) obs: 1.2 / Num. unique obs: 729 / Rrim(I) all: 0.894 / % possible all: 97.4 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS / Resolution: 2.63→72.87 Å / Cor.coef. Fo:Fc: 0.906 / Cor.coef. Fo:Fc free: 0.905 / SU R Cruickshank DPI: 0.79 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.365 / SU Rfree Blow DPI: 0.266 / SU Rfree Cruickshank DPI: 0.256
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Displacement parameters | Biso mean: 58.38 Å2
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Refine analyze | Luzzati coordinate error obs: 0.43 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Resolution: 2.63→72.87 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.63→2.82 Å / Total num. of bins used: 8
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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