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- PDB-4x7k: Co-crystal Structure of PERK bound to 4-{2-amino-3-[5-fluoro-2-(m... -
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Open data
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Basic information
Entry | Database: PDB / ID: 4x7k | ||||||
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Title | Co-crystal Structure of PERK bound to 4-{2-amino-3-[5-fluoro-2-(methylamino)quinazolin-6-yl]-4-methylbenzoyl}-1-methyl-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one inhibitor | ||||||
![]() | Eukaryotic translation initiation factor 2-alpha kinase 3,Eukaryotic translation initiation factor 2-alpha kinase 3 | ||||||
![]() | TRANSFERASE/TRANSFERASE INHIBITOR / CATALYTIC DOMAIN / TRANSFERASE-TRANSFERASE INHIBITOR / COMPLEX / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
Function / homology | ![]() regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation / negative regulation of translation in response to stress / regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / regulation of translational initiation by eIF2 alpha phosphorylation / eiF2alpha phosphorylation in response to endoplasmic reticulum stress / chondrocyte development / eukaryotic translation initiation factor 2alpha kinase activity / response to manganese-induced endoplasmic reticulum stress / negative regulation of translational initiation in response to stress / PERK-mediated unfolded protein response ...regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation / negative regulation of translation in response to stress / regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / regulation of translational initiation by eIF2 alpha phosphorylation / eiF2alpha phosphorylation in response to endoplasmic reticulum stress / chondrocyte development / eukaryotic translation initiation factor 2alpha kinase activity / response to manganese-induced endoplasmic reticulum stress / negative regulation of translational initiation in response to stress / PERK-mediated unfolded protein response / PERK regulates gene expression / negative regulation of myelination / endocrine pancreas development / ALK mutants bind TKIs / endoplasmic reticulum organization / cellular response to cold / positive regulation of transcription by RNA polymerase I / ER overload response / bone mineralization / positive regulation of vascular endothelial growth factor production / cellular response to glucose starvation / endoplasmic reticulum unfolded protein response / negative regulation of translational initiation / cellular response to amino acid starvation / response to endoplasmic reticulum stress / ossification / insulin-like growth factor receptor signaling pathway / skeletal system development / calcium-mediated signaling / Hsp90 protein binding / positive regulation of protein localization to nucleus / activation of cysteine-type endopeptidase activity involved in apoptotic process / KEAP1-NFE2L2 pathway / Signaling by ALK fusions and activated point mutants / peptidyl-serine phosphorylation / protein phosphatase binding / angiogenesis / protein autophosphorylation / negative regulation of translation / non-specific serine/threonine protein kinase / protein kinase activity / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / positive regulation of gene expression / endoplasmic reticulum membrane / perinuclear region of cytoplasm / enzyme binding / endoplasmic reticulum / ATP binding / identical protein binding / membrane / nucleus / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Shaffer, P.L. / Long, A.M. / Chen, H. | ||||||
![]() | ![]() Title: Discovery of 1H-Pyrazol-3(2H)-ones as Potent and Selective Inhibitors of Protein Kinase R-like Endoplasmic Reticulum Kinase (PERK). Authors: Smith, A.L. / Andrews, K.L. / Beckmann, H. / Bellon, S.F. / Beltran, P.J. / Booker, S. / Chen, H. / Chung, Y.A. / D'Angelo, N.D. / Dao, J. / Dellamaggiore, K.R. / Jaeckel, P. / Kendall, R. / ...Authors: Smith, A.L. / Andrews, K.L. / Beckmann, H. / Bellon, S.F. / Beltran, P.J. / Booker, S. / Chen, H. / Chung, Y.A. / D'Angelo, N.D. / Dao, J. / Dellamaggiore, K.R. / Jaeckel, P. / Kendall, R. / Labitzke, K. / Long, A.M. / Materna-Reichelt, S. / Mitchell, P. / Norman, M.H. / Powers, D. / Rose, M. / Shaffer, P.L. / Wu, M.M. / Lipford, J.R. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 132.4 KB | Display | ![]() |
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PDB format | ![]() | 99.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 726.7 KB | Display | ![]() |
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Full document | ![]() | 728.2 KB | Display | |
Data in XML | ![]() | 14.7 KB | Display | |
Data in CIF | ![]() | 21.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 4x7hC ![]() 4x7jSC ![]() 4x7lC ![]() 4x7nC ![]() 4x7oC S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components on special symmetry positions |
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Components
#1: Protein | Mass: 36816.363 Da / Num. of mol.: 1 / Mutation: D937N, Deletion of 670-874 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: Q9NZJ5, non-specific serine/threonine protein kinase |
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#2: Chemical | ChemComp-3Z3 / |
#3: Chemical | ChemComp-TLA / |
#4: Chemical | ChemComp-GOL / |
#5: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.92 Å3/Da / Density % sol: 57.86 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7 Details: 0.18M Na/K Tartrate, 5% PEG-3350, 0.1M HEPES pH 7.0 |
-Data collection
Diffraction | Mean temperature: 80 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: ![]() ![]() ![]() | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Jun 6, 2011 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9774 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.8→50 Å / Num. obs: 41166 / % possible obs: 100 % / Redundancy: 10.4 % / Rmerge(I) obs: 0.102 / Χ2: 1.112 / Net I/av σ(I): 26.78 / Net I/σ(I): 8.3 / Num. measured all: 426553 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1 / Rejects: _ / % possible all: 100
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 4X7J Resolution: 1.8→40.88 Å / Cor.coef. Fo:Fc: 0.966 / Cor.coef. Fo:Fc free: 0.959 / SU B: 3.976 / SU ML: 0.059 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.094 / ESU R Free: 0.091 / Stereochemistry target values: MAXIMUM LIKELIHOOD / 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: 1.4 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 68.41 Å2 / Biso mean: 30.17 Å2 / Biso min: 9.99 Å2
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Refinement step | Cycle: final / Resolution: 1.8→40.88 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.801→1.848 Å / Total num. of bins used: 20
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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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