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Yorodumi- PDB-5hx6: Crystal structure of RIP1 kinase with a benzo[b][1,4]oxazepin-4-one -
+Open data
-Basic information
Entry | Database: PDB / ID: 5hx6 | ||||||
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Title | Crystal structure of RIP1 kinase with a benzo[b][1,4]oxazepin-4-one | ||||||
Components | Receptor-interacting serine/threonine-protein kinase 1 | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / Kinase / inhibitor complex / non-hinge binding / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
Function / homology | Function and homology information regulation of ATP:ADP antiporter activity / ripoptosome assembly / positive regulation of interleukin-6-mediated signaling pathway / positive regulation of miRNA processing / ripoptosome assembly involved in necroptotic process / death domain binding / ripoptosome / Defective RIPK1-mediated regulated necrosis / TRIF-mediated programmed cell death / TLR3-mediated TICAM1-dependent programmed cell death ...regulation of ATP:ADP antiporter activity / ripoptosome assembly / positive regulation of interleukin-6-mediated signaling pathway / positive regulation of miRNA processing / ripoptosome assembly involved in necroptotic process / death domain binding / ripoptosome / Defective RIPK1-mediated regulated necrosis / TRIF-mediated programmed cell death / TLR3-mediated TICAM1-dependent programmed cell death / Microbial modulation of RIPK1-mediated regulated necrosis / Regulation by c-FLIP / CASP8 activity is inhibited / Dimerization of procaspase-8 / programmed necrotic cell death / TNF signaling / Caspase activation via Death Receptors in the presence of ligand / T cell apoptotic process / positive regulation of macrophage differentiation / SARS-CoV-1-mediated effects on programmed cell death / necroptotic signaling pathway / JUN kinase kinase kinase activity / peptidyl-serine autophosphorylation / NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 / positive regulation of necroptotic process / death-inducing signaling complex / RIP-mediated NFkB activation via ZBP1 / negative regulation of necroptotic process / positive regulation of tumor necrosis factor-mediated signaling pathway / death receptor binding / TRP channels / positive regulation of extrinsic apoptotic signaling pathway / positive regulation of programmed cell death / positive regulation of programmed necrotic cell death / TNFR1-induced proapoptotic signaling / RIPK1-mediated regulated necrosis / positive regulation of execution phase of apoptosis / necroptotic process / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / response to tumor necrosis factor / signaling adaptor activity / negative regulation of canonical NF-kappaB signal transduction / extrinsic apoptotic signaling pathway / tumor necrosis factor-mediated signaling pathway / TICAM1, RIP1-mediated IKK complex recruitment / IKK complex recruitment mediated by RIP1 / TNFR1-induced NF-kappa-B signaling pathway / positive regulation of interleukin-8 production / negative regulation of extrinsic apoptotic signaling pathway / Regulation of TNFR1 signaling / positive regulation of JNK cascade / protein catabolic process / Regulation of necroptotic cell death / cellular response to hydrogen peroxide / cellular response to growth factor stimulus / positive regulation of inflammatory response / positive regulation of non-canonical NF-kappaB signal transduction / positive regulation of neuron apoptotic process / positive regulation of reactive oxygen species metabolic process / Ovarian tumor domain proteases / positive regulation of tumor necrosis factor production / cellular response to tumor necrosis factor / positive regulation of NF-kappaB transcription factor activity / positive regulation of canonical NF-kappaB signal transduction / response to oxidative stress / amyloid fibril formation / Potential therapeutics for SARS / protein autophosphorylation / receptor complex / endosome membrane / non-specific serine/threonine protein kinase / Ub-specific processing proteases / protein kinase activity / intracellular signal transduction / inflammatory response / positive regulation of protein phosphorylation / positive regulation of apoptotic process / protein serine kinase activity / protein serine/threonine kinase activity / apoptotic process / ubiquitin protein ligase binding / protein-containing complex binding / positive regulation of gene expression / negative regulation of apoptotic process / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / protein-containing complex / mitochondrion / ATP binding / identical protein binding / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.23 Å | ||||||
Authors | Campobasso, N. / Ward, P. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2016 Title: DNA-Encoded Library Screening Identifies Benzo[b][1,4]oxazepin-4-ones as Highly Potent and Monoselective Receptor Interacting Protein 1 Kinase Inhibitors. Authors: Harris, P.A. / King, B.W. / Bandyopadhyay, D. / Berger, S.B. / Campobasso, N. / Capriotti, C.A. / Cox, J.A. / Dare, L. / Dong, X. / Finger, J.N. / Grady, L.C. / Hoffman, S.J. / Jeong, J.U. / ...Authors: Harris, P.A. / King, B.W. / Bandyopadhyay, D. / Berger, S.B. / Campobasso, N. / Capriotti, C.A. / Cox, J.A. / Dare, L. / Dong, X. / Finger, J.N. / Grady, L.C. / Hoffman, S.J. / Jeong, J.U. / Kang, J. / Kasparcova, V. / Lakdawala, A.S. / Lehr, R. / McNulty, D.E. / Nagilla, R. / Ouellette, M.T. / Pao, C.S. / Rendina, A.R. / Schaeffer, M.C. / Summerfield, J.D. / Swift, B.A. / Totoritis, R.D. / Ward, P. / Zhang, A. / Zhang, D. / Marquis, R.W. / Bertin, J. / Gough, P.J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5hx6.cif.gz | 208.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5hx6.ent.gz | 170.4 KB | Display | PDB format |
PDBx/mmJSON format | 5hx6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/hx/5hx6 ftp://data.pdbj.org/pub/pdb/validation_reports/hx/5hx6 | HTTPS FTP |
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-Related structure data
Similar structure data |
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-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 34596.891 Da / Num. of mol.: 2 / Fragment: residues 1-294 / Mutation: C34A,C127A,C233A, C240A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RIPK1, RIP, RIP1 / Production host: Baculovirus expression vector pFastBac1-HM References: UniProt: Q13546, non-specific serine/threonine protein 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: 2.04 Å3/Da / Density % sol: 39.84 % |
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Crystal grow | Temperature: 310 K / Method: vapor diffusion / pH: 7.5 Details: Well solution 26 % PEG 4K, 0.1 M HEPES pH 7.5; co-crystallized with NEC-4 and cmpd 8 back soaked into crystals at 5mM concentration Cryo was transfer 6 % to 25 % glycerol added to well solution |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 21-ID-D / Wavelength: 1.078 Å |
Detector | Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Oct 3, 2013 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.078 Å / Relative weight: 1 |
Reflection | Resolution: 2.23→131 Å / Num. obs: 28389 / % possible obs: 99.4 % / Redundancy: 4.8 % / Biso Wilson estimate: 43.53 Å2 / Net I/σ(I): 15.2 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.23→80.18 Å / Cor.coef. Fo:Fc: 0.927 / Cor.coef. Fo:Fc free: 0.8901 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.265 / SU Rfree Blow DPI: 0.209
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Displacement parameters | Biso mean: 53.63 Å2
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Refine analyze | Luzzati coordinate error obs: 0.272 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.23→80.18 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.23→2.31 Å / Total num. of bins used: 14
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