Entry | Database: PDB / ID: 4zth |
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Title | Structure of human p38aMAPK-arylpyridazinylpyridine fragment complex used in inhibitor discovery |
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Components | Mitogen-activated protein kinase 14 |
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Keywords | TRANSFERASE |
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Function / homology | Function and homology information
positive regulation of cyclase activity / stress-activated protein kinase signaling cascade / Activation of PPARGC1A (PGC-1alpha) by phosphorylation / CD163 mediating an anti-inflammatory response / regulation of synaptic membrane adhesion / stress-induced premature senescence / cell surface receptor protein serine/threonine kinase signaling pathway / 3'-UTR-mediated mRNA stabilization / KSRP (KHSRP) binds and destabilizes mRNA / cartilage condensation ...positive regulation of cyclase activity / stress-activated protein kinase signaling cascade / Activation of PPARGC1A (PGC-1alpha) by phosphorylation / CD163 mediating an anti-inflammatory response / regulation of synaptic membrane adhesion / stress-induced premature senescence / cell surface receptor protein serine/threonine kinase signaling pathway / 3'-UTR-mediated mRNA stabilization / KSRP (KHSRP) binds and destabilizes mRNA / cartilage condensation / positive regulation of myoblast fusion / cellular response to UV-B / Platelet sensitization by LDL / mitogen-activated protein kinase p38 binding / positive regulation of muscle cell differentiation / positive regulation of myotube differentiation / NFAT protein binding / Myogenesis / glucose import / Activation of the AP-1 family of transcription factors / negative regulation of hippo signaling / regulation of cytokine production involved in inflammatory response / ERK/MAPK targets / p38MAPK cascade / fatty acid oxidation / cellular response to lipoteichoic acid / MAP kinase kinase activity / response to dietary excess / response to muramyl dipeptide / RHO GTPases Activate NADPH Oxidases / MAP kinase activity / regulation of ossification / cellular response to vascular endothelial growth factor stimulus / mitogen-activated protein kinase / signal transduction in response to DNA damage / positive regulation of myoblast differentiation / chondrocyte differentiation / vascular endothelial growth factor receptor signaling pathway / stress-activated MAPK cascade / skeletal muscle tissue development / positive regulation of cardiac muscle cell proliferation / lipopolysaccharide-mediated signaling pathway / negative regulation of inflammatory response to antigenic stimulus / p38MAPK events / striated muscle cell differentiation / response to muscle stretch / positive regulation of interleukin-12 production / positive regulation of brown fat cell differentiation / osteoclast differentiation / positive regulation of erythrocyte differentiation / DNA damage checkpoint signaling / activated TAK1 mediates p38 MAPK activation / cellular response to ionizing radiation / positive regulation of glucose import / stem cell differentiation / NOD1/2 Signaling Pathway / response to insulin / bone development / negative regulation of canonical Wnt signaling pathway / placenta development / cell morphogenesis / platelet activation / cellular response to virus / VEGFA-VEGFR2 Pathway / spindle pole / positive regulation of protein import into nucleus / osteoblast differentiation / ADP signalling through P2Y purinoceptor 1 / glucose metabolic process / chemotaxis / positive regulation of reactive oxygen species metabolic process / cellular senescence / cellular response to tumor necrosis factor / peptidyl-serine phosphorylation / cellular response to lipopolysaccharide / protein phosphatase binding / angiogenesis / secretory granule lumen / Oxidative Stress Induced Senescence / Regulation of TP53 Activity through Phosphorylation / ficolin-1-rich granule lumen / transcription by RNA polymerase II / cell surface receptor signaling pathway / intracellular signal transduction / nuclear speck / protein serine kinase activity / protein serine/threonine kinase activity / glutamatergic synapse / apoptotic process / Neutrophil degranulation / positive regulation of gene expression / regulation of transcription by RNA polymerase II / enzyme binding / signal transduction / positive regulation of transcription by RNA polymerase II / mitochondrion / extracellular region / nucleoplasm / ATP binding / nucleusSimilarity search - Function Mitogen-activated protein kinase 14 / Mitogen-activated protein (MAP) kinase p38-like / : / Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase signature. / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Protein kinase domain ...Mitogen-activated protein kinase 14 / Mitogen-activated protein (MAP) kinase p38-like / : / Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase signature. / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha BetaSimilarity search - Domain/homology BETA-MERCAPTOETHANOL / 4-[3-(4-FLUOROPHENYL)-1H-PYRAZOL-4-YL]PYRIDINE / 6-chloro-3-phenyl-4-(pyridin-4-yl)pyridazine / Mitogen-activated protein kinase 14Similarity search - Component |
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Biological species | Homo sapiens (human) |
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Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.15 Å |
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Authors | Grum-Tokars, V.L. / Roy, S.M. / Watterson, D.M. |
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Funding support | United States, 4items Organization | Grant number | Country |
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National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) | U01AG043415 | United States | National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) | R01NS056051 | United States | National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) | R01AG031311 | United States | National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) | R01NS093920 | United States |
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Citation | Journal: J.Med.Chem. / Year: 2019 Title: A Selective and Brain Penetrant p38 alpha MAPK Inhibitor Candidate for Neurologic and Neuropsychiatric Disorders That Attenuates Neuroinflammation and Cognitive Dysfunction. Authors: Roy, S.M. / Minasov, G. / Arancio, O. / Chico, L.W. / Van Eldik, L.J. / Anderson, W.F. / Pelletier, J.C. / Watterson, D.M. |
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History | Deposition | May 14, 2015 | Deposition site: RCSB / Processing site: RCSB |
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Revision 1.0 | Jun 22, 2016 | Provider: repository / Type: Initial release |
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Revision 1.1 | Sep 20, 2017 | Group: Author supporting evidence / Derived calculations / Category: pdbx_audit_support / pdbx_struct_oper_list Item: _pdbx_audit_support.funding_organization / _pdbx_struct_oper_list.symmetry_operation |
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Revision 1.2 | Jan 1, 2020 | Group: Author supporting evidence / Database references / Category: citation / citation_author / pdbx_audit_support Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year |
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Revision 1.3 | Mar 6, 2024 | Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2 Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession |
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