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Yorodumi- PDB-4u6r: Crystal structure of human IRE1 cytoplasmic domains in complex wi... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4u6r | ||||||
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Title | Crystal structure of human IRE1 cytoplasmic domains in complex with a sulfonamide inhibitor. | ||||||
Components | Serine/threonine-protein kinase/endoribonuclease IRE1 | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / Transferase / Kinase / Hydrolase / Endoribonuclease / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
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 / platelet-derived growth factor receptor binding ...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 / platelet-derived growth factor receptor binding / Hydrolases; Acting on ester bonds; Endoribonucleases producing 5'-phosphomonoesters / 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 / cellular response to vascular endothelial growth factor stimulus / cellular response to unfolded protein / regulation of macroautophagy / positive regulation of JUN kinase activity / positive regulation of vascular associated smooth muscle cell proliferation / RNA endonuclease activity / Hsp70 protein binding / response to endoplasmic reticulum stress / positive regulation of RNA splicing / cellular response to glucose stimulus / Hsp90 protein binding / ADP 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: 2.5 Å | ||||||
Authors | Mohr, C. | ||||||
Citation | Journal: Acs Med.Chem.Lett. / Year: 2015 Title: Unfolded Protein Response in Cancer: IRE1 alpha Inhibition by Selective Kinase Ligands Does Not Impair Tumor Cell Viability. Authors: Harrington, P.E. / Biswas, K. / Malwitz, D. / Tasker, A.S. / Mohr, C. / Andrews, K.L. / Dellamaggiore, K. / Kendall, R. / Beckmann, H. / Jaeckel, P. / Materna-Reichelt, S. / Allen, J.R. / Lipford, J.R. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4u6r.cif.gz | 184.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4u6r.ent.gz | 143 KB | Display | PDB format |
PDBx/mmJSON format | 4u6r.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4u6r_validation.pdf.gz | 751 KB | Display | wwPDB validaton report |
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Full document | 4u6r_full_validation.pdf.gz | 759.3 KB | Display | |
Data in XML | 4u6r_validation.xml.gz | 18.5 KB | Display | |
Data in CIF | 4u6r_validation.cif.gz | 25.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/u6/4u6r ftp://data.pdbj.org/pub/pdb/validation_reports/u6/4u6r | HTTPS FTP |
-Related structure data
Related structure data | 4u79C 3p23S 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
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 52374.629 Da / Num. of mol.: 1 / Fragment: UNP residues 547-977 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ERN1, IRE1 / Production host: Trichoplusia ni (cabbage looper) References: UniProt: O75460, non-specific serine/threonine protein kinase |
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-Non-polymers , 5 types, 90 molecules
#2: Chemical | ChemComp-3E4 / | ||||||
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#3: Chemical | ChemComp-SO4 / #4: Chemical | ChemComp-EDO / | #5: Chemical | ChemComp-EPE / | #6: Water | ChemComp-HOH / | |
-Details
Sequence details | SER TO THR CONFLICT AT THIS POSITION IN UNP ENTRY O75460 |
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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: 2.91 Å3/Da / Density % sol: 57.75 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: 0.2M Ammonium sulfate, 0.1M HEPES, 25% PEG3350, pH7.5 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU FR-E SUPERBRIGHT / Wavelength: 1.5418 Å |
Detector | Type: RIGAKU SATURN 944 / Detector: CCD / Date: Sep 1, 2011 |
Radiation | Monochromator: VariMax HF / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 2.5→29.47 Å / Num. obs: 21786 / % possible obs: 98.8 % / Redundancy: 7.3 % / Rmerge(I) obs: 0.089 / Net I/σ(I): 9.7 |
Reflection shell | Resolution: 2.5→2.59 Å / Redundancy: 7.4 % / Rmerge(I) obs: 0.457 / Mean I/σ(I) obs: 4.52 / % possible all: 97.7 |
-Processing
Software | Name: REFMAC / Version: 5.8.0049 / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3P23 Resolution: 2.5→29.47 Å / Cor.coef. Fo:Fc: 0.939 / Cor.coef. Fo:Fc free: 0.913 / SU B: 15.495 / SU ML: 0.173 / Cross valid method: THROUGHOUT / ESU R: 0.37 / ESU R Free: 0.258 Stereochemistry target values: MAXIMUM LIKELIHOOD WITH PHASES Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 43.874 Å2
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Refinement step | Cycle: 1 / Resolution: 2.5→29.47 Å
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