+Open data
-Basic information
Entry | Database: PDB / ID: 5j8i | ||||||
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Title | Crystal structure of TL11-113 bound to TAK1-TAB1 | ||||||
Components | Mitogen-activated protein kinase kinase kinase 7/TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 chimera | ||||||
Keywords | TRANSFERASE/TRANSFERASE inhibitor / Mitogen-activated protein kinase kinase kinase 7/TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 / TRANSFERASE-TRANSFERASE inhibitor complex | ||||||
Function / homology | Function and homology information histone kinase activity / nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / positive regulation of cGAS/STING signaling pathway / interleukin-17A-mediated signaling pathway / MAP kinase kinase kinase kinase activity / linear polyubiquitin binding / cardiac septum development / I-kappaB phosphorylation / mitogen-activated protein kinase kinase kinase / toll-like receptor 3 signaling pathway ...histone kinase activity / nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / positive regulation of cGAS/STING signaling pathway / interleukin-17A-mediated signaling pathway / MAP kinase kinase kinase kinase activity / linear polyubiquitin binding / cardiac septum development / I-kappaB phosphorylation / mitogen-activated protein kinase kinase kinase / toll-like receptor 3 signaling pathway / interleukin-33-mediated signaling pathway / TRIF-dependent toll-like receptor signaling pathway / type II transforming growth factor beta receptor binding / coronary vasculature development / ATAC complex / cellular response to angiotensin / positive regulation of vascular associated smooth muscle cell migration / aorta development / cytoplasmic pattern recognition receptor signaling pathway / anoikis / interleukin-1-mediated signaling pathway / MyD88-dependent toll-like receptor signaling pathway / non-canonical NF-kappaB signal transduction / toll-like receptor 4 signaling pathway / protein serine/threonine phosphatase activity / mitogen-activated protein kinase p38 binding / stimulatory C-type lectin receptor signaling pathway / p38MAPK cascade / Fc-epsilon receptor signaling pathway / positive regulation of macroautophagy / positive regulation of cell size / MAP kinase kinase kinase activity / MAP kinase activity / positive regulation of cell cycle / canonical NF-kappaB signal transduction / heart morphogenesis / stress-activated MAPK cascade / protein serine/threonine kinase binding / positive regulation of JUN kinase activity / positive regulation of vascular associated smooth muscle cell proliferation / JNK cascade / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / TICAM1,TRAF6-dependent induction of TAK1 complex / positive regulation of interleukin-2 production / TRAF6-mediated induction of TAK1 complex within TLR4 complex / protein serine/threonine kinase activator activity / transforming growth factor beta receptor signaling pathway / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / TNFR1-induced NF-kappa-B signaling pathway / activated TAK1 mediates p38 MAPK activation / Activation of NF-kappaB in B cells / lung development / NOD1/2 Signaling Pathway / TAK1-dependent IKK and NF-kappa-B activation / positive regulation of protein serine/threonine kinase activity / positive regulation of T cell cytokine production / receptor tyrosine kinase binding / CLEC7A (Dectin-1) signaling / transcription coactivator binding / FCERI mediated NF-kB activation / Interleukin-1 signaling / positive regulation of non-canonical NF-kappaB signal transduction / MAPK cascade / Downstream TCR signaling / cellular response to tumor necrosis factor / Ca2+ pathway / T cell receptor signaling pathway / cellular response to hypoxia / scaffold protein binding / positive regulation of canonical NF-kappaB signal transduction / DNA-binding transcription factor binding / in utero embryonic development / positive regulation of MAPK cascade / molecular adaptor activity / endosome membrane / Ub-specific processing proteases / defense response to bacterium / nuclear speck / inflammatory response / immune response / negative regulation of gene expression / protein serine kinase activity / protein serine/threonine kinase activity / ubiquitin protein ligase binding / endoplasmic reticulum membrane / protein-containing complex binding / SARS-CoV-2 activates/modulates innate and adaptive immune responses / magnesium ion binding / endoplasmic reticulum / protein-containing complex / ATP binding / identical protein binding / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.404 Å | ||||||
Authors | Gurbani, D. / Westover, K.D. | ||||||
Funding support | United States, 1items
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Citation | Journal: Bioorg. Med. Chem. / Year: 2017 Title: Structure-guided development of covalent TAK1 inhibitors. Authors: Tan, L. / Gurbani, D. / Weisberg, E.L. / Hunter, J.C. / Li, L. / Jones, D.S. / Ficarro, S.B. / Mowafy, S. / Tam, C.P. / Rao, S. / Du, G. / Griffin, J.D. / Sorger, P.K. / Marto, J.A. / Westover, K.D. / Gray, N.S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5j8i.cif.gz | 122.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5j8i.ent.gz | 95.1 KB | Display | PDB format |
PDBx/mmJSON format | 5j8i.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/j8/5j8i ftp://data.pdbj.org/pub/pdb/validation_reports/j8/5j8i | HTTPS FTP |
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-Related structure data
Related structure data | 5e7rC 5j7sC 5j9lC 5jh6C 5jk3C 2yiyS 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
#1: Protein | Mass: 35463.867 Da / Num. of mol.: 1 Fragment: UNP O43318 residues 31-303, Q15750 residues 468-504 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MAP3K7, TAK1, TAB1, MAP3K7IP1 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: O43318, UniProt: Q15750, mitogen-activated protein kinase kinase kinase |
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#2: Chemical | ChemComp-6H4 / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.97 Å3/Da / Density % sol: 69.02 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7 Details: 0.75M NaCitrate, 0.1M Tris-HCL, 0.2M NaCl, pH 7.0, 5mM Adenosine; |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.97932 Å |
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Oct 15, 2015 |
Radiation | Monochromator: Rosenbaum-Rock high-resolution double-crystal monochromator Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97932 Å / Relative weight: 1 |
Reflection | Resolution: 2.43→50 Å / Num. obs: 21238 / % possible obs: 96.3 % / Redundancy: 8.3 % / Rmerge(I) obs: 0.124 / Net I/σ(I): 18.94 |
Reflection shell | Resolution: 2.43→2.47 Å / Redundancy: 5.6 % / Rmerge(I) obs: 1.571 / Mean I/σ(I) obs: 1.16 / % possible all: 80.1 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2YIY Resolution: 2.404→49.081 Å / SU ML: 0.36 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 33.58 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.404→49.081 Å
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Refine LS restraints |
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LS refinement shell |
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