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Yorodumi- PDB-6rn8: RIP2 Kinase Catalytic Domain complex with 2(4[(1,3benzothiazol5yl... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6rn8 | ||||||
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Title | RIP2 Kinase Catalytic Domain complex with 2(4[(1,3benzothiazol5yl)amino]6(2methylpropane2sulfonyl)quinazolin7yl)oxy)ethyl phosphate | ||||||
Components | Receptor-interacting serine/threonine-protein kinase 2 | ||||||
Keywords | TRANSFERASE / Kinase / Structure Based drug discovery | ||||||
Function / homology | Function and homology information response to interleukin-18 / positive regulation of T-helper 1 cell differentiation / toll-like receptor 2 signaling pathway / positive regulation of cytokine-mediated signaling pathway / immature T cell proliferation in thymus / positive regulation of T-helper 1 type immune response / positive regulation of xenophagy / LIM domain binding / xenophagy / nucleotide-binding oligomerization domain containing 1 signaling pathway ...response to interleukin-18 / positive regulation of T-helper 1 cell differentiation / toll-like receptor 2 signaling pathway / positive regulation of cytokine-mediated signaling pathway / immature T cell proliferation in thymus / positive regulation of T-helper 1 type immune response / positive regulation of xenophagy / LIM domain binding / xenophagy / nucleotide-binding oligomerization domain containing 1 signaling pathway / CD4-positive, alpha-beta T cell proliferation / positive regulation of protein K63-linked ubiquitination / positive regulation of stress-activated MAPK cascade / caspase binding / cellular response to muramyl dipeptide / CARD domain binding / positive regulation of immature T cell proliferation in thymus / JUN kinase kinase kinase activity / cellular response to peptidoglycan / response to interleukin-12 / positive regulation of CD4-positive, alpha-beta T cell proliferation / activation of cysteine-type endopeptidase activity / nucleotide-binding oligomerization domain containing 2 signaling pathway / positive regulation of macrophage cytokine production / toll-like receptor 4 signaling pathway / response to exogenous dsRNA / cellular response to lipoteichoic acid / positive regulation of interferon-alpha production / canonical NF-kappaB signal transduction / signaling adaptor activity / stress-activated MAPK cascade / positive regulation of chemokine production / JNK cascade / lipopolysaccharide-mediated signaling pathway / ERK1 and ERK2 cascade / positive regulation of interleukin-12 production / p75NTR recruits signalling complexes / positive regulation of interleukin-2 production / positive regulation of interferon-beta production / response to interleukin-1 / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / positive regulation of peptidyl-threonine phosphorylation / positive regulation of interleukin-1 beta production / positive regulation of protein ubiquitination / activated TAK1 mediates p38 MAPK activation / positive regulation of JNK cascade / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / TAK1-dependent IKK and NF-kappa-B activation / NOD1/2 Signaling Pathway / protein homooligomerization / cytokine-mediated signaling pathway / Interleukin-1 signaling / positive regulation of interleukin-6 production / positive regulation of type II interferon production / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of peptidyl-serine phosphorylation / positive regulation of tumor necrosis factor production / Ovarian tumor domain proteases / Downstream TCR signaling / positive regulation of protein binding / positive regulation of NF-kappaB transcription factor activity / T cell receptor signaling pathway / positive regulation of canonical NF-kappaB signal transduction / adaptive immune response / vesicle / 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 / protein serine kinase activity / innate immune response / protein serine/threonine kinase activity / signaling receptor binding / apoptotic process / SARS-CoV-2 activates/modulates innate and adaptive immune responses / signal transduction / endoplasmic reticulum / positive regulation of transcription by RNA polymerase II / protein homodimerization activity / protein-containing complex / ATP binding / identical protein binding / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.69 Å | ||||||
Authors | Convery, M.A. / Haile, P.A. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2019 Title: Discovery of a First-in-Class Receptor Interacting Protein 2 (RIP2) Kinase Specific Clinical Candidate, 2-((4-(Benzo[d]thiazol-5-ylamino)-6-(tert-butylsulfonyl)quinazolin-7-yl)oxy)ethyl ...Title: Discovery of a First-in-Class Receptor Interacting Protein 2 (RIP2) Kinase Specific Clinical Candidate, 2-((4-(Benzo[d]thiazol-5-ylamino)-6-(tert-butylsulfonyl)quinazolin-7-yl)oxy)ethyl Dihydrogen Phosphate, for the Treatment of Inflammatory Diseases. Authors: Haile, P.A. / Casillas, L.N. / Votta, B.J. / Wang, G.Z. / Charnley, A.K. / Dong, X. / Bury, M.J. / Romano, J.J. / Mehlmann, J.F. / King, B.W. / Erhard, K.F. / Hanning, C.R. / Lipshutz, D.B. ...Authors: Haile, P.A. / Casillas, L.N. / Votta, B.J. / Wang, G.Z. / Charnley, A.K. / Dong, X. / Bury, M.J. / Romano, J.J. / Mehlmann, J.F. / King, B.W. / Erhard, K.F. / Hanning, C.R. / Lipshutz, D.B. / Desai, B.M. / Capriotti, C.A. / Schaeffer, M.C. / Berger, S.B. / Mahajan, M.K. / Reilly, M.A. / Nagilla, R. / Rivera, E.J. / Sun, H.H. / Kenna, J.K. / Beal, A.M. / Ouellette, M.T. / Kelly, M. / Stemp, G. / Convery, M.A. / Vossenkamper, A. / MacDonald, T.T. / Gough, P.J. / Bertin, J. / Marquis, R.W. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6rn8.cif.gz | 252.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6rn8.ent.gz | 203.1 KB | Display | PDB format |
PDBx/mmJSON format | 6rn8.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6rn8_validation.pdf.gz | 1003.3 KB | Display | wwPDB validaton report |
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Full document | 6rn8_full_validation.pdf.gz | 1005 KB | Display | |
Data in XML | 6rn8_validation.xml.gz | 25 KB | Display | |
Data in CIF | 6rn8_validation.cif.gz | 36.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rn/6rn8 ftp://data.pdbj.org/pub/pdb/validation_reports/rn/6rn8 | HTTPS FTP |
-Related structure data
Related structure data | 6rnaC 5ar4S S: Starting model for refinement C: citing same article (ref.) |
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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: 35682.977 Da / Num. of mol.: 2 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: Chemical | ChemComp-CA / | #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: 3.79 Å3/Da / Density % sol: 67.56 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5 Details: Morpheus G2. 0.1M Carboxylic acids, 0.1M buffer system 1 pH6.5, 50% Precipitant Mix 2 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.98 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: May 3, 2012 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.98 Å / Relative weight: 1 |
Reflection | Resolution: 2.69→78.32 Å / Num. obs: 30432 / % possible obs: 100 % / Redundancy: 6.2 % / Biso Wilson estimate: 58.6 Å2 / Rmerge(I) obs: 0.132 / Net I/σ(I): 12.7 |
Reflection shell | Resolution: 2.69→2.76 Å / Rmerge(I) obs: 0.835 / Mean I/σ(I) obs: 2.8 / Num. unique obs: 2189 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: 5AR4 Resolution: 2.69→34.19 Å / Cor.coef. Fo:Fc: 0.935 / Cor.coef. Fo:Fc free: 0.913 / SU R Cruickshank DPI: 0.325 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.343 / SU Rfree Blow DPI: 0.231 / SU Rfree Cruickshank DPI: 0.23
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Displacement parameters | Biso mean: 50.27 Å2
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Refine analyze | Luzzati coordinate error obs: 0.3 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Resolution: 2.69→34.19 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.69→2.71 Å / Total num. of bins used: 50
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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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