+Open data
-Basic information
Entry | Database: PDB / ID: 5nhp | ||||||
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Title | Human Erk2 with an Erk1/2 inhibitor | ||||||
Components | Mitogen-activated protein kinase 1 | ||||||
Keywords | TRANSFERASE / Erk2 / kinase / inhibitor / oncology | ||||||
Function / homology | Function and homology information 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 / cytosine metabolic process / ERKs are inactivated ...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 / cytosine metabolic process / ERKs are inactivated / 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 / Signaling by LTK in cancer / 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 / positive regulation of macrophage chemotaxis / ERBB2-ERBB3 signaling pathway / lung morphogenesis / 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 / : / positive regulation of telomere capping / Recycling pathway of L1 / MAPK1 (ERK2) activation / Bergmann glial cell differentiation / thyroid gland development / negative regulation of cell differentiation / Advanced glycosylation endproduct receptor signaling / steroid hormone receptor signaling pathway / Transcriptional and post-translational regulation of MITF-M expression and activity / 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 telomere maintenance via telomerase / cellular response to cadmium ion / NPAS4 regulates expression of target genes / ERK1 and ERK2 cascade / myelination / NCAM signaling for neurite out-growth / phosphotyrosine residue binding / cellular response to amino acid starvation / 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 / Signal transduction by L1 / Regulation of PTEN gene transcription / caveola / long-term synaptic potentiation / Negative regulation of FGFR3 signaling / FCERI mediated MAPK activation / Negative regulation of FGFR2 signaling / Downregulation of SMAD2/3:SMAD4 transcriptional activity / FCGR3A-mediated phagocytosis / Negative regulation of FGFR4 signaling / Negative regulation of FGFR1 signaling / B cell receptor signaling pathway / peptidyl-threonine phosphorylation / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / 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 Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / Resolution: 1.99 Å | ||||||
Authors | Debreczeni, J.E. / Ward, R.A. / Bethel, P. / Cook, C. / Davies, E. / Eckersley, K. / Fairley, G. / Feron, L. / Flemington, V. / Graham, M.A. ...Debreczeni, J.E. / Ward, R.A. / Bethel, P. / Cook, C. / Davies, E. / Eckersley, K. / Fairley, G. / Feron, L. / Flemington, V. / Graham, M.A. / Greenwood, R. / Hopcroft, P. / Howard, T.D. / Hudson, J. / James, M. / Jones, C.D. / Jones, C.R. / Lamont, S. / Lewis, R. / Lindsay, N. / Roberts, K. / Simpson, I. / StGallay, S. / Swallow, S. / Tonge, M. | ||||||
Citation | Journal: J. Med. Chem. / Year: 2017 Title: Structure-Guided Discovery of Potent and Selective Inhibitors of ERK1/2 from a Modestly Active and Promiscuous Chemical Start Point. Authors: Ward, R.A. / Bethel, P. / Cook, C. / Davies, E. / Debreczeni, J.E. / Fairley, G. / Feron, L. / Flemington, V. / Graham, M.A. / Greenwood, R. / Griffin, N. / Hanson, L. / Hopcroft, P. / ...Authors: Ward, R.A. / Bethel, P. / Cook, C. / Davies, E. / Debreczeni, J.E. / Fairley, G. / Feron, L. / Flemington, V. / Graham, M.A. / Greenwood, R. / Griffin, N. / Hanson, L. / Hopcroft, P. / Howard, T.D. / Hudson, J. / James, M. / Jones, C.D. / Jones, C.R. / Lamont, S. / Lewis, R. / Lindsay, N. / Roberts, K. / Simpson, I. / St-Gallay, S. / Swallow, S. / Tang, J. / Tonge, M. / Wang, Z. / Zhai, B. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5nhp.cif.gz | 155.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5nhp.ent.gz | 120 KB | Display | PDB format |
PDBx/mmJSON format | 5nhp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/nh/5nhp ftp://data.pdbj.org/pub/pdb/validation_reports/nh/5nhp | HTTPS FTP |
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-Related structure data
Related structure data | 5nguC 5nhfC 5nhhC 5nhjC 5nhlC 5nhoC 5nhvC 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: 43909.297 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MAPK1, ERK2, PRKM1, PRKM2 / Production host: Escherichia coli (E. coli) References: UniProt: P28482, mitogen-activated protein kinase | ||||
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#2: Chemical | #3: Chemical | ChemComp-8XK / | #4: 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: 2.52 Å3/Da / Density % sol: 51.1 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop Details: 30% PegMME2K, 100mM HEPES pH 7.6, 200mM Ammonium sulfate |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID29 / Wavelength: 0.979 Å |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Jun 16, 2014 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.979 Å / Relative weight: 1 |
Reflection | Resolution: 1.99→45.54 Å / Num. obs: 26082 / % possible obs: 97.8 % / Redundancy: 3.3 % / Biso Wilson estimate: 32.82 Å2 / Rmerge(I) obs: 0.078 / Rsym value: 0.078 / Net I/σ(I): 11.5 |
Reflection shell | Resolution: 1.994→2.001 Å / Redundancy: 3.2 % / Rmerge(I) obs: 0.688 / Mean I/σ(I) obs: 2.2 / Rsym value: 0.688 / % possible all: 94.8 |
-Processing
Software |
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Refinement | Resolution: 1.99→44.46 Å / Cor.coef. Fo:Fc: 0.94 / Cor.coef. Fo:Fc free: 0.901 / Rfactor Rfree error: 0 / SU R Cruickshank DPI: 0.18 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.183 / SU Rfree Blow DPI: 0.149 / SU Rfree Cruickshank DPI: 0.149
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Displacement parameters | Biso mean: 35.2 Å2
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Refine analyze | Luzzati coordinate error obs: 0.27 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.99→44.46 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.99→2.07 Å / Rfactor Rfree error: 0 / Total num. of bins used: 13
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Refinement TLS params. | Method: refined / Origin x: -6.0234 Å / Origin y: 8.6615 Å / Origin z: 47.5601 Å
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Refinement TLS group | Selection details: { A|* } |