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- PDB-6g91: Fragment-based discovery of a highly potent, orally bioavailable ... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6g91 | ||||||
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Title | Fragment-based discovery of a highly potent, orally bioavailable inhibitor which modulates the phosphorylation and catalytic activity of ERK1/2 | ||||||
![]() | Mitogen-activated protein kinase 1 | ||||||
![]() | SIGNALING PROTEIN / Erk2 Kinase inhibitor | ||||||
Function / homology | ![]() phospho-PLA2 pathway / Signaling by MAPK mutants / 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 / cytosine metabolic process ...phospho-PLA2 pathway / Signaling by MAPK mutants / 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 / cytosine metabolic process / response to epidermal growth factor / Signaling by MAP2K mutants / Signaling by NODAL / RSK activation / Golgi Cisternae Pericentriolar Stack Reorganization / positive regulation of macrophage proliferation / Regulation of the apoptosome activity / outer ear morphogenesis / regulation of cellular pH / regulation of Golgi inheritance / ERBB signaling pathway / labyrinthine layer blood vessel development / mammary gland epithelial cell proliferation / 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 / lung morphogenesis / positive regulation of macrophage chemotaxis / ERBB2-ERBB3 signaling pathway / response to exogenous dsRNA / regulation of cytoskeleton organization / Activation of the AP-1 family of transcription factors / face development / ERK/MAPK targets / progesterone receptor signaling pathway / androgen receptor signaling pathway / RUNX2 regulates osteoblast differentiation / pseudopodium / Recycling pathway of L1 / MAPK1 (ERK2) activation / Bergmann glial cell differentiation / negative regulation of cell differentiation / positive regulation of telomere capping / thyroid gland development / Advanced glycosylation endproduct receptor signaling / steroid hormone receptor signaling pathway / 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 attenuation / Estrogen-stimulated signaling through PRKCZ / Nuclear events stimulated by ALK signaling in cancer / Schwann cell development / Growth hormone receptor signaling / stress-activated MAPK cascade / lipopolysaccharide-mediated signaling pathway / positive regulation of telomerase activity / positive regulation of telomere maintenance via telomerase / cellular response to cadmium ion / NPAS4 regulates expression of target genes / ERK1 and ERK2 cascade / cellular response to amino acid starvation / myelination / NCAM signaling for neurite out-growth / phosphotyrosine residue binding / RNA polymerase II CTD heptapeptide repeat kinase activity / ESR-mediated signaling / insulin-like growth factor receptor signaling pathway / thymus development / positive regulation of peptidyl-threonine phosphorylation / Regulation of PTEN gene transcription / Signal transduction by L1 / caveola / long-term synaptic potentiation / Negative regulation of FGFR3 signaling / Downregulation of SMAD2/3:SMAD4 transcriptional activity / Negative regulation of FGFR2 signaling / FCERI mediated MAPK activation / Negative regulation of FGFR4 signaling / FCGR3A-mediated phagocytosis / Negative regulation of FGFR1 signaling / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / B cell receptor signaling pathway / peptidyl-threonine phosphorylation / Spry regulation of FGF signaling / Signaling by high-kinase activity BRAF mutants / response to nicotine / MAP2K and MAPK activation / regulation of protein stability / Oncogene Induced Senescence / mitotic spindle / Regulation of actin dynamics for phagocytic cup formation Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() | ||||||
![]() | O'Reilly, M. | ||||||
![]() | ![]() Title: Fragment-Based Discovery of a Potent, Orally Bioavailable Inhibitor That Modulates the Phosphorylation and Catalytic Activity of ERK1/2. Authors: Heightman, T.D. / Berdini, V. / Braithwaite, H. / Buck, I.M. / Cassidy, M. / Castro, J. / Courtin, A. / Day, J.E.H. / East, C. / Fazal, L. / Graham, B. / Griffiths-Jones, C.M. / Lyons, J.F. ...Authors: Heightman, T.D. / Berdini, V. / Braithwaite, H. / Buck, I.M. / Cassidy, M. / Castro, J. / Courtin, A. / Day, J.E.H. / East, C. / Fazal, L. / Graham, B. / Griffiths-Jones, C.M. / Lyons, J.F. / Martins, V. / Muench, S. / Munck, J.M. / Norton, D. / O'Reilly, M. / Palmer, N. / Pathuri, P. / Reader, M. / Rees, D.C. / Rich, S.J. / Richardson, C. / Saini, H. / Thompson, N.T. / Wallis, N.G. / Walton, H. / Wilsher, N.E. / Woolford, A.J. / Cooke, M. / Cousin, D. / Onions, S. / Shannon, J. / Watts, J. / Murray, C.W. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 164.1 KB | Display | ![]() |
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PDB format | ![]() | 131.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 682.3 KB | Display | ![]() |
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Full document | ![]() | 682.7 KB | Display | |
Data in XML | ![]() | 19.1 KB | Display | |
Data in CIF | ![]() | 29.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6g8xC ![]() 6g92C ![]() 6g93C ![]() 6g97C ![]() 6g9aC ![]() 6g9dC ![]() 6g9hC ![]() 6g9jC ![]() 6g9kC ![]() 6g9mC ![]() 6g9nC ![]() 6gdmC ![]() 6gdqC ![]() 6ge0C 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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1 |
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Unit cell |
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Components
#1: Protein | Mass: 42551.922 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P28482, mitogen-activated protein kinase | ||||
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#2: Chemical | #3: Chemical | ChemComp-EQW / | #4: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.31 Å3/Da / Density % sol: 46.71 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7.2 Details: 0.1M HEPES/NaOHpH=7.2, 34.0%w/v MPEG 2000, 0.02M Mercaptoethanol, 0.2M (NH4)2SO4 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ![]() |
Detector | Type: DECTRIS PILATUS 300K / Detector: PIXEL / Date: Feb 4, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54178 Å / Relative weight: 1 |
Reflection | Resolution: 1.796→46.02 Å / Num. obs: 34922 / % possible obs: 96.7 % / Redundancy: 2.6 % / Biso Wilson estimate: 23.39 Å2 / Rrim(I) all: 0.057 / Net I/av σ(I): 11.3 / Net I/σ(I): 11.3 |
Reflection shell | Resolution: 1.8→1.82 Å / Rmerge(I) obs: 0.41 / Num. unique obs: 919 / Rrim(I) all: 0.41 / % possible all: 83.1 |
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Processing
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Refinement | Method to determine structure: ![]()
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Displacement parameters | Biso mean: 31.708 Å2
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Refine analyze | Luzzati coordinate error obs: 0.21 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Resolution: 1.8→44.36 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.8→1.85 Å / Total num. of bins used: 17
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Refinement TLS params. | Method: refined / Origin x: -1.0668 Å / Origin y: 3.6553 Å / Origin z: 38.1309 Å
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Refinement TLS group | Selection details: { A|8 - A|357 } |