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Yorodumi- PDB-6hv0: IRE1 kinase/RNase in complex with imidazo[1,2-b]pyridazin-8-amine... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6hv0 | ||||||||||||
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Title | IRE1 kinase/RNase in complex with imidazo[1,2-b]pyridazin-8-amine compound 33 | ||||||||||||
Components | Serine/threonine-protein kinase/endoribonuclease IRE1 | ||||||||||||
Keywords | SIGNALING PROTEIN / Unfolded Protein Response Allosteric inhibitor | ||||||||||||
Function / homology | Function and homology information peptidyl-serine trans-autophosphorylation / mRNA splicing, via endonucleolytic cleavage and ligation / AIP1-IRE1 complex / Ire1 complex / IRE1alpha activates chaperones / IRE1-TRAF2-ASK1 complex / insulin metabolic process / peptidyl-serine autophosphorylation / IRE1-RACK1-PP2A complex / Hydrolases; Acting on ester bonds; Endoribonucleases producing 5'-phosphomonoesters ...peptidyl-serine trans-autophosphorylation / mRNA splicing, via endonucleolytic cleavage and ligation / AIP1-IRE1 complex / Ire1 complex / IRE1alpha activates chaperones / IRE1-TRAF2-ASK1 complex / insulin metabolic process / peptidyl-serine autophosphorylation / IRE1-RACK1-PP2A complex / Hydrolases; Acting on ester bonds; Endoribonucleases producing 5'-phosphomonoesters / platelet-derived growth factor receptor binding / positive regulation of endoplasmic reticulum unfolded protein response / endothelial cell proliferation / nuclear inner membrane / IRE1-mediated unfolded protein response / mRNA catabolic process / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / regulation of macroautophagy / cellular response to vascular endothelial growth factor stimulus / cellular response to unfolded protein / positive regulation of JUN kinase activity / RNA endonuclease activity / positive regulation of vascular associated smooth muscle cell proliferation / Hsp70 protein binding / response to endoplasmic reticulum stress / positive regulation of RNA splicing / ADP binding / cellular response to glucose stimulus / Hsp90 protein binding / cellular response to hydrogen peroxide / unfolded protein binding / protein autophosphorylation / non-specific serine/threonine protein kinase / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / endoplasmic reticulum membrane / enzyme binding / magnesium ion binding / endoplasmic reticulum / protein homodimerization activity / mitochondrion / ATP binding / identical protein binding / cytoplasm Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.73 Å | ||||||||||||
Authors | Bayliss, R. / Bhatia, C. / Collins, I. | ||||||||||||
Funding support | United Kingdom, 3items
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Citation | Journal: J.Med.Chem. / Year: 2019 Title: Binding to an Unusual Inactive Kinase Conformation by Highly Selective Inhibitors of Inositol-Requiring Enzyme 1 alpha Kinase-Endoribonuclease. Authors: Colombano, G. / Caldwell, J.J. / Matthews, T.P. / Bhatia, C. / Joshi, A. / McHardy, T. / Mok, N.Y. / Newbatt, Y. / Pickard, L. / Strover, J. / Hedayat, S. / Walton, M.I. / Myers, S.M. / ...Authors: Colombano, G. / Caldwell, J.J. / Matthews, T.P. / Bhatia, C. / Joshi, A. / McHardy, T. / Mok, N.Y. / Newbatt, Y. / Pickard, L. / Strover, J. / Hedayat, S. / Walton, M.I. / Myers, S.M. / Jones, A.M. / Saville, H. / McAndrew, C. / Burke, R. / Eccles, S.A. / Davies, F.E. / Bayliss, R. / Collins, I. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6hv0.cif.gz | 92.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6hv0.ent.gz | 66.9 KB | Display | PDB format |
PDBx/mmJSON format | 6hv0.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/hv/6hv0 ftp://data.pdbj.org/pub/pdb/validation_reports/hv/6hv0 | HTTPS FTP |
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-Related structure data
Related structure data | 6hx1C 4z7gS 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: 47755.820 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ERN1, IRE1 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: O75460, non-specific serine/threonine protein kinase, Hydrolases; Acting on ester bonds; Endoribonucleases producing 5'-phosphomonoesters |
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#2: Chemical | ChemComp-GUK / |
#3: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.77 Å3/Da / Density % sol: 55.53 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop Details: 20% polyethylene glycol 3350, 0.2 M sodium acetate and 0.1 bis-tris propane (pH 6.5) |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.54 Å |
Detector | Type: RIGAKU SATURN 944 / Detector: CCD / Date: Oct 4, 2014 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54 Å / Relative weight: 1 |
Reflection | Resolution: 2.73→40.4 Å / Num. obs: 14150 / % possible obs: 99.2 % / Redundancy: 3.5 % / CC1/2: 0.986 / Rrim(I) all: 0.167 / Net I/σ(I): 17.5 |
Reflection shell | Resolution: 2.73→2.86 Å / Redundancy: 2.7 % / Mean I/σ(I) obs: 1.8 / Num. unique obs: 1770 / CC1/2: 0.584 / Rrim(I) all: 0.742 / % possible all: 94.8 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4Z7G Resolution: 2.73→32.967 Å / SU ML: 0.37 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 28.18
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.73→32.967 Å
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Refine LS restraints |
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LS refinement shell |
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