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Open data
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Basic information
Entry | Database: PDB / ID: 5e7r | ||||||
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Title | Crystal structure of TL10-81 bound to TAK1-TAB1 | ||||||
![]() | TAK1 kinase - TAB1 chimera fusion protein | ||||||
![]() | 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 | ![]() histone kinase activity / positive regulation of cGAS/STING signaling pathway / nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / MAP kinase kinase kinase kinase activity / linear polyubiquitin binding / interleukin-17A-mediated signaling pathway / cardiac septum development / I-kappaB phosphorylation / mitogen-activated protein kinase kinase kinase / interleukin-33-mediated signaling pathway ...histone kinase activity / positive regulation of cGAS/STING signaling pathway / nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / MAP kinase kinase kinase kinase activity / linear polyubiquitin binding / interleukin-17A-mediated signaling pathway / cardiac septum development / I-kappaB phosphorylation / mitogen-activated protein kinase kinase kinase / interleukin-33-mediated signaling pathway / toll-like receptor 3 signaling pathway / type II transforming growth factor beta receptor binding / TRIF-dependent toll-like receptor signaling pathway / coronary vasculature development / ATAC complex / cellular response to angiotensin / positive regulation of vascular associated smooth muscle cell migration / anoikis / aorta development / interleukin-1-mediated signaling pathway / MyD88-dependent toll-like receptor signaling pathway / non-canonical NF-kappaB signal transduction / toll-like receptor 4 signaling pathway / cytoplasmic pattern recognition receptor signaling pathway / protein serine/threonine phosphatase activity / mitogen-activated protein kinase p38 binding / p38MAPK cascade / stimulatory C-type lectin receptor signaling pathway / 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 / heart morphogenesis / canonical NF-kappaB signal transduction / protein serine/threonine kinase binding / stress-activated MAPK cascade / JNK cascade / positive regulation of JUN kinase activity / positive regulation of vascular associated smooth muscle cell proliferation / 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 / TAK1-dependent IKK and NF-kappa-B activation / NOD1/2 Signaling Pathway / 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 / DNA-binding transcription factor binding / positive regulation of canonical NF-kappaB signal transduction / in utero embryonic development / positive regulation of MAPK cascade / molecular adaptor activity / endosome membrane / Ub-specific processing proteases / nuclear speck / defense response to bacterium / 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 | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Gurbani, D. / Hunter, J.C. / Tan, L. / Chen, Z. / Westover, K.D. | ||||||
Funding support | ![]()
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![]() | ![]() 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: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 117.8 KB | Display | ![]() |
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PDB format | ![]() | 90.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 5j7sC ![]() 5j8iC ![]() 5j9lC ![]() 5jh6C ![]() 5jk3C ![]() 2yiyS S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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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, UNP Q15750 residues 468-504 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: O43318, UniProt: Q15750, mitogen-activated protein kinase kinase kinase |
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#2: Chemical | ChemComp-5KW / |
#3: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 4.07 Å3/Da / Density % sol: 69.77 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7 Details: 0.65-0.75 M sodium citrate pH 7.0, 0.2 M NaCl, 0.1 M Tris pH 7.0, and 5mM adenosine. Adenosine bound TAK1-TAB1 crystals are backsoaked with inhibitor |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Oct 16, 2014 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97918 Å / Relative weight: 1 |
Reflection | Resolution: 2.1→50 Å / Num. obs: 32105 / % possible obs: 96.7 % / Redundancy: 8 % / Rmerge(I) obs: 0.235 / Rpim(I) all: 0.088 / Net I/σ(I): 6.3 |
Reflection shell | Resolution: 2.1→2.14 Å / Redundancy: 6.4 % / Mean I/σ(I) obs: 1.7 / CC1/2: 0.561 / Rpim(I) all: 0.553 / % possible all: 98.4 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 2YIY Resolution: 2.11→42.148 Å / SU ML: 0.24 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 28.66 / 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: 2.11→42.148 Å
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Refine LS restraints |
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LS refinement shell |
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