[English] 日本語
Yorodumi- PDB-4qtb: Structure of human ERK1 in complex with SCH772984 revealing a nov... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4qtb | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of human ERK1 in complex with SCH772984 revealing a novel inhibitor-induced binding pocket | ||||||
Components | Mitogen-activated protein kinase 3 | ||||||
Keywords | Transferase/transferase inhibitor / Structural Genomics / Structural Genomics Consortium / SGC / TRANSFERASE / kinase / MAPK / signalling / inhibitor / allosteric / Structural Genomics Consortium (SGC) / Transferase-transferase inhibitor complex | ||||||
Function / homology | Function and homology information positive regulation of xenophagy / xenophagy / RAF-independent MAPK1/3 activation / Suppression of apoptosis / Signaling by Activin / Gastrin-CREB signalling pathway via PKC and MAPK / cardiac neural crest cell development involved in heart development / caveolin-mediated endocytosis / ERKs are inactivated / response to epidermal growth factor ...positive regulation of xenophagy / xenophagy / RAF-independent MAPK1/3 activation / Suppression of apoptosis / Signaling by Activin / Gastrin-CREB signalling pathway via PKC and MAPK / cardiac neural crest cell development involved in heart development / caveolin-mediated endocytosis / ERKs are inactivated / response to epidermal growth factor / Signaling by MAP2K mutants / Signaling by NODAL / RSK activation / Golgi Cisternae Pericentriolar Stack Reorganization / regulation of cellular pH / positive regulation of macrophage proliferation / positive regulation of cyclase activity / outer ear morphogenesis / Regulation of the apoptosome activity / cartilage development / regulation of Golgi inheritance / interleukin-1-mediated signaling pathway / trachea formation / Negative feedback regulation of MAPK pathway / regulation of early endosome to late endosome transport / regulation of stress-activated MAPK cascade / IFNG signaling activates MAPKs / Frs2-mediated activation / positive regulation of macrophage chemotaxis / lung morphogenesis / ERBB2-ERBB3 signaling pathway / response to exogenous dsRNA / regulation of cytoskeleton organization / Activation of the AP-1 family of transcription factors / face development / MAPK3 (ERK1) activation / ERK/MAPK targets / pseudopodium / RUNX2 regulates osteoblast differentiation / Bergmann glial cell differentiation / positive regulation of telomere capping / thyroid gland development / Advanced glycosylation endproduct receptor signaling / RHO GTPases Activate NADPH Oxidases / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / Regulation of HSF1-mediated heat shock response / MAP kinase activity / regulation of ossification / RHO GTPases Activate WASPs and WAVEs / mitogen-activated protein kinase / phosphatase binding / signal transduction in response to DNA damage / Nuclear events stimulated by ALK signaling in cancer / Signal attenuation / BMP signaling pathway / Schwann cell development / stress-activated MAPK cascade / Growth hormone receptor signaling / peptidyl-tyrosine autophosphorylation / lipopolysaccharide-mediated signaling pathway / positive regulation of telomerase activity / sensory perception of pain / negative regulation of TORC1 signaling / cellular response to cadmium ion / positive regulation of telomere maintenance via telomerase / ERK1 and ERK2 cascade / NPAS4 regulates expression of target genes / cellular response to amino acid starvation / myelination / RNA Polymerase I Promoter Opening / NCAM signaling for neurite out-growth / phosphotyrosine residue binding / ESR-mediated signaling / insulin-like growth factor receptor signaling pathway / thymus development / Regulation of PTEN gene transcription / Signal transduction by L1 / caveola / Negative regulation of FGFR3 signaling / Downregulation of SMAD2/3:SMAD4 transcriptional activity / FCERI mediated MAPK activation / Negative regulation of FGFR2 signaling / FCGR3A-mediated phagocytosis / Negative regulation of FGFR4 signaling / Negative regulation of FGFR1 signaling / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / Spry regulation of FGF signaling / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / modulation of chemical synaptic transmission / Oncogene Induced Senescence / Regulation of actin dynamics for phagocytic cup formation / ISG15 antiviral mechanism / cellular response to reactive oxygen species / cellular response to mechanical stimulus / Negative regulation of MAPK pathway / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.4 Å | ||||||
Authors | Chaikuad, A. / Keates, T. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. / Bountra, C. / Knapp, S. / Structural Genomics Consortium (SGC) | ||||||
Citation | Journal: Nat.Chem.Biol. / Year: 2014 Title: A unique inhibitor binding site in ERK1/2 is associated with slow binding kinetics. Authors: Chaikuad, A. / M C Tacconi, E. / Zimmer, J. / Liang, Y. / Gray, N.S. / Tarsounas, M. / Knapp, S. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 4qtb.cif.gz | 319.9 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb4qtb.ent.gz | 259.1 KB | Display | PDB format |
PDBx/mmJSON format | 4qtb.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qt/4qtb ftp://data.pdbj.org/pub/pdb/validation_reports/qt/4qtb | HTTPS FTP |
---|
-Related structure data
Related structure data | 4qtaC 4qtcC 4qtdC 4qteC 2zoqS C: citing same article (ref.) S: Starting model for refinement |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
2 |
| ||||||||
Unit cell |
|
-Components
-Protein , 1 types, 2 molecules AB
#1: Protein | Mass: 43277.566 Da / Num. of mol.: 2 / Fragment: kinase domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ERK1, MAPK3, PRKM3 / Plasmid: pNIC28-Bsa4 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21-R3-pRARE2 References: UniProt: P27361, mitogen-activated protein kinase |
---|
-Non-polymers , 6 types, 1141 molecules
#2: Chemical | ChemComp-EDO / #3: Chemical | #4: Chemical | #5: Chemical | #6: Chemical | #7: Water | ChemComp-HOH / | |
---|
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.2 Å3/Da / Density % sol: 44.06 % |
---|---|
Crystal grow | Temperature: 277.15 K / Method: vapor diffusion, sitting drop / pH: 8 Details: 33% PEG4000, 0.1 M Tris pH 8.0 and 0.2 M lithium sulphate, VAPOR DIFFUSION, SITTING DROP, temperature 277.15K |
-Data collection
Diffraction | Mean temperature: 100 K |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.91997 Å |
Detector | Type: PSI PILATUS 6M / Detector: PIXEL / Date: Oct 5, 2013 / Details: Kirkpatrick Baez bimorph mirror pair |
Radiation | Monochromator: Si (111) double crystal monochromator / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.91997 Å / Relative weight: 1 |
Reflection | Resolution: 1.4→38.15 Å / Num. all: 140419 / Num. obs: 140385 / % possible obs: 95.8 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 4.1 % / Biso Wilson estimate: 9.8 Å2 / Rmerge(I) obs: 0.089 / Net I/σ(I): 8.8 |
Reflection shell | Resolution: 1.4→1.48 Å / Redundancy: 3.9 % / Rmerge(I) obs: 0.618 / Mean I/σ(I) obs: 2.2 / Num. unique all: 19971 / % possible all: 93.3 |
-Processing
Software |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: pdb entry 2ZOQ Resolution: 1.4→32.74 Å / Cor.coef. Fo:Fc: 0.976 / Cor.coef. Fo:Fc free: 0.967 / SU B: 1.892 / SU ML: 0.039 / Cross valid method: THROUGHOUT / σ(F): 0 / σ(I): 2 / ESU R: 0.056 / ESU R Free: 0.059 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 16.182 Å2
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine analyze | Luzzati coordinate error obs: 0.143 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.4→32.74 Å
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 1.4→1.436 Å / Total num. of bins used: 20
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS group |
|