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Yorodumi- PDB-5j7b: The identification and pharmacological characterization of 6-(ter... -
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-Basic information
Entry | Database: PDB / ID: 5j7b | ||||||
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Title | The identification and pharmacological characterization of 6-(tert-butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine (GSK583), a highly potent and selective inhibitor of RIP2 Kinase, GSK583 complex | ||||||
Components | Receptor-interacting serine/threonine-protein kinase 2 | ||||||
Keywords | Transferase/Transferase Inhibitor / kinase domain / kinase inhibitor / structure-based drug design / inhibitor selectivity / Transferase-Transferase Inhibitor complex | ||||||
Function / homology | Function and homology information response to interleukin-18 / positive regulation of T-helper 1 cell differentiation / toll-like receptor 2 signaling pathway / caspase binding / cellular response to muramyl dipeptide / positive regulation of cytokine-mediated signaling pathway / immature T cell proliferation in thymus / positive regulation of T-helper 1 type immune response / CARD domain binding / positive regulation of xenophagy ...response to interleukin-18 / positive regulation of T-helper 1 cell differentiation / toll-like receptor 2 signaling pathway / caspase binding / cellular response to muramyl dipeptide / positive regulation of cytokine-mediated signaling pathway / immature T cell proliferation in thymus / positive regulation of T-helper 1 type immune response / CARD domain binding / positive regulation of xenophagy / xenophagy / LIM domain binding / nucleotide-binding oligomerization domain containing 1 signaling pathway / positive regulation of protein K63-linked ubiquitination / positive regulation of stress-activated MAPK cascade / CD4-positive, alpha-beta T cell proliferation / positive regulation of immature T cell proliferation in thymus / JUN kinase kinase kinase activity / cellular response to peptidoglycan / response to interleukin-12 / activation of cysteine-type endopeptidase activity / positive regulation of CD4-positive, alpha-beta T cell proliferation / nucleotide-binding oligomerization domain containing 2 signaling pathway / positive regulation of macrophage cytokine production / toll-like receptor 4 signaling pathway / response to exogenous dsRNA / positive regulation of interferon-alpha production / cellular response to lipoteichoic acid / canonical NF-kappaB signal transduction / signaling adaptor activity / lipopolysaccharide-mediated signaling pathway / stress-activated MAPK cascade / positive regulation of chemokine production / JNK cascade / positive regulation of interleukin-12 production / positive regulation of interferon-beta production / p75NTR recruits signalling complexes / positive regulation of interleukin-2 production / ERK1 and ERK2 cascade / response to interleukin-1 / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / positive regulation of interleukin-1 beta production / positive regulation of peptidyl-threonine phosphorylation / positive regulation of protein ubiquitination / activated TAK1 mediates p38 MAPK activation / non-specific protein-tyrosine kinase / positive regulation of JNK cascade / non-membrane spanning protein tyrosine kinase activity / NOD1/2 Signaling Pathway / TAK1-dependent IKK and NF-kappa-B activation / protein homooligomerization / cytokine-mediated signaling pathway / positive regulation of interleukin-6 production / Interleukin-1 signaling / positive regulation of type II interferon production / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of tumor necrosis factor production / Ovarian tumor domain proteases / Downstream TCR signaling / positive regulation of protein binding / positive regulation of peptidyl-serine phosphorylation / positive regulation of NF-kappaB transcription factor activity / T cell receptor signaling pathway / positive regulation of canonical NF-kappaB signal transduction / vesicle / adaptive immune response / positive regulation of ERK1 and ERK2 cascade / cytoskeleton / non-specific serine/threonine protein kinase / defense response to Gram-positive bacterium / defense response to bacterium / inflammatory response / positive regulation of apoptotic process / innate immune response / signaling receptor binding / protein serine kinase activity / protein serine/threonine kinase activity / apoptotic process / SARS-CoV-2 activates/modulates innate and adaptive immune responses / signal transduction / endoplasmic reticulum / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / protein-containing complex / ATP binding / identical protein binding / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.53 Å | ||||||
Authors | Convery, M.A. / Casillas, L.N. / Haile, P.A. / Votta, B.J. / Lakdawala, A.S. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2016 Title: The Identification and Pharmacological Characterization of 6-(tert-Butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine (GSK583), a Highly Potent and Selective Inhibitor of RIP2 Kinase. Authors: Haile, P.A. / Votta, B.J. / Marquis, R.W. / Bury, M.J. / Mehlmann, J.F. / Singhaus, R. / Charnley, A.K. / Lakdawala, A.S. / Convery, M.A. / Lipshutz, D.B. / Desai, B.M. / Swift, B. / ...Authors: Haile, P.A. / Votta, B.J. / Marquis, R.W. / Bury, M.J. / Mehlmann, J.F. / Singhaus, R. / Charnley, A.K. / Lakdawala, A.S. / Convery, M.A. / Lipshutz, D.B. / Desai, B.M. / Swift, B. / Capriotti, C.A. / Berger, S.B. / Mahajan, M.K. / Reilly, M.A. / Rivera, E.J. / Sun, H.H. / Nagilla, R. / Beal, A.M. / Finger, J.N. / Cook, M.N. / King, B.W. / Ouellette, M.T. / Totoritis, R.D. / Pierdomenico, M. / Negroni, A. / Stronati, L. / Cucchiara, S. / Ziokowski, B. / Vossenkamper, A. / MacDonald, T.T. / Gough, P.J. / Bertin, J. / Casillas, L.N. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5j7b.cif.gz | 134.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5j7b.ent.gz | 103.6 KB | Display | PDB format |
PDBx/mmJSON format | 5j7b.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5j7b_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 5j7b_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 5j7b_validation.xml.gz | 24.1 KB | Display | |
Data in CIF | 5j7b_validation.cif.gz | 34.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/j7/5j7b ftp://data.pdbj.org/pub/pdb/validation_reports/j7/5j7b | HTTPS FTP |
-Related structure data
Related structure data | 5j79C 5ar4S 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: 37605.980 Da / Num. of mol.: 2 / Fragment: UNP residues 1-310 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RIPK2, CARDIAK, RICK, RIP2, UNQ277/PRO314/PRO34092 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: O43353, non-specific serine/threonine protein kinase, non-specific protein-tyrosine kinase #2: Chemical | #3: 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: 3.61 Å3/Da / Density % sol: 65.91 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion / pH: 7 Details: 100mM Mes pH7, 12% PEG 400, 250mM CaCl2. Crystals soaked in compound for 2 hours. |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.95 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Jan 20, 2011 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.95 Å / Relative weight: 1 |
Reflection | Resolution: 2.53→78.33 Å / Num. obs: 36582 / % possible obs: 99.9 % / Redundancy: 6 % / Rmerge(I) obs: 0.095 / Net I/σ(I): 12.9 |
Reflection shell | Resolution: 2.53→2.67 Å / Redundancy: 6 % / Rmerge(I) obs: 0.385 / Mean I/σ(I) obs: 4 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: 5ar4 Resolution: 2.53→20 Å / Cor.coef. Fo:Fc: 0.96 / Cor.coef. Fo:Fc free: 0.931 / SU B: 7.392 / SU ML: 0.161 / Cross valid method: THROUGHOUT / ESU R: 0.257 / ESU R Free: 0.223
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 70.473 Å2
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Refinement step | Cycle: 1 / Resolution: 2.53→20 Å
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Refine LS restraints |
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