Entry Database : PDB / ID : 4anb Structure visualization Downloads & linksTitle Crystal structures of human MEK1 with carboxamide-based allosteric inhibitor XL518 (GDC-0973), or related analogs. ComponentsDUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 1 Details Keywords TRANSFERASE / MAP2K1 / ATP-BINDING / ALLOSTERIC INHIBITIONFunction / homology Function and homology informationFunction Domain/homology Component
epithelial cell proliferation involved in lung morphogenesis / negative regulation of homotypic cell-cell adhesion / negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway / positive regulation of endodermal cell differentiation / regulation of vascular associated smooth muscle contraction / mitogen-activated protein kinase kinase / Golgi inheritance / placenta blood vessel development / MAP-kinase scaffold activity / positive regulation of muscle contraction ... epithelial cell proliferation involved in lung morphogenesis / negative regulation of homotypic cell-cell adhesion / negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway / positive regulation of endodermal cell differentiation / regulation of vascular associated smooth muscle contraction / mitogen-activated protein kinase kinase / Golgi inheritance / placenta blood vessel development / MAP-kinase scaffold activity / positive regulation of muscle contraction / labyrinthine layer development / regulation of axon regeneration / cerebellar cortex formation / melanosome transport / type B pancreatic cell proliferation / central nervous system neuron differentiation / Signaling by MAP2K mutants / vesicle transport along microtubule / positive regulation of axonogenesis / positive regulation of Ras protein signal transduction / regulation of Golgi inheritance / mitogen-activated protein kinase kinase kinase binding / triglyceride homeostasis / trachea formation / Negative feedback regulation of MAPK pathway / regulation of early endosome to late endosome transport / regulation of stress-activated MAPK cascade / Frs2-mediated activation / MAPK3 (ERK1) activation / ERBB2-ERBB3 signaling pathway / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / endodermal cell differentiation / face development / MAP kinase kinase activity / positive regulation of ATP biosynthetic process / Bergmann glial cell differentiation / Uptake and function of anthrax toxins / thyroid gland development / protein kinase activator activity / positive regulation of protein serine/threonine kinase activity / response to axon injury / Schwann cell development / keratinocyte differentiation / MAP3K8 (TPL2)-dependent MAPK1/3 activation / neuron projection morphogenesis / ERK1 and ERK2 cascade / myelination / positive regulation of autophagy / protein serine/threonine/tyrosine kinase activity / dendrite cytoplasm / insulin-like growth factor receptor signaling pathway / response to glucocorticoid / thymus development / protein serine/threonine kinase activator activity / Signal transduction by L1 / cell motility / positive regulation of transcription elongation by RNA polymerase II / RAF activation / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / small GTPase binding / chemotaxis / neuron differentiation / 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 / Signaling by BRAF and RAF1 fusions / cellular senescence / MAPK cascade / late endosome / heart development / scaffold protein binding / protein tyrosine kinase activity / cell cortex / perikaryon / response to oxidative stress / microtubule / early endosome / positive regulation of ERK1 and ERK2 cascade / protein kinase activity / postsynaptic density / ciliary basal body / positive regulation of cell migration / axon / negative regulation of cell population proliferation / negative regulation of gene expression / protein serine kinase activity / focal adhesion / protein serine/threonine kinase activity / intracellular membrane-bounded organelle / centrosome / positive regulation of gene expression / protein-containing complex binding / positive regulation of DNA-templated transcription / perinuclear region of cytoplasm / glutamatergic synapse / endoplasmic reticulum / Golgi apparatus / signal transduction Similarity search - Function : / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site ... : / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / 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 Beta Similarity search - Domain/homology PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER / Chem-YQY / Dual specificity mitogen-activated protein kinase kinase 1 Similarity search - ComponentBiological species HOMO SAPIENS (human)Method X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution : 2.2 Å DetailsAuthors Rice, K.D. / Aay, N. / Anand, N.K. / Blazey, C.M. / Bowles, O.J. / Bussenius, J. / Costanzo, S. / Curtis, J.K. / Defina, S.C. / Dubenko, L. ...Rice, K.D. / Aay, N. / Anand, N.K. / Blazey, C.M. / Bowles, O.J. / Bussenius, J. / Costanzo, S. / Curtis, J.K. / Defina, S.C. / Dubenko, L. / Engst, S. / Joshi, A.A. / Kennedy, A.R. / Kim, A.I. / Koltun, E.S. / Lougheed, J.C. / Manalo, J.C.L. / Martini, J.F. / Nuss, J.M. / Peto, C.J. / Tsang, T.H. / Yu, P. / Johnston, S. CitationJournal : Acs Med.Chem.Lett. / Year : 2012Title : Novel Carboxamide-Based Allosteric Mek Inhibitors: Discovery and Optimization Efforts Toward Xl518 (Gdc-0973)Authors: Rice, K.D. / Aay, N. / Anand, N.K. / Blazey, C.M. / Bowles, O.J. / Bussenius, J. / Costanzo, S. / Curtis, J.K. / Defina, S.C. / Dubenko, L. / Engst, S. / Joshi, A.A. / Kennedy, A.R. / Kim, A. ... Authors : Rice, K.D. / Aay, N. / Anand, N.K. / Blazey, C.M. / Bowles, O.J. / Bussenius, J. / Costanzo, S. / Curtis, J.K. / Defina, S.C. / Dubenko, L. / Engst, S. / Joshi, A.A. / Kennedy, A.R. / Kim, A.I. / Koltun, E.S. / Lougheed, J.C. / Manalo, J.C.L. / Martini, J.F. / Nuss, J.M. / Peto, C.J. / Tsang, T.H. / Yu, P. / Johnston, S. History Deposition Mar 16, 2012 Deposition site : PDBE / Processing site : PDBERevision 1.0 Dec 19, 2012 Provider : repository / Type : Initial releaseRevision 1.1 Jun 18, 2014 Group : Database referencesRevision 2.0 Jun 20, 2018 Group : Advisory / Atomic model ... Advisory / Atomic model / Data collection / Derived calculations Category : atom_site / pdbx_nonpoly_scheme ... atom_site / pdbx_nonpoly_scheme / pdbx_struct_conn_angle / pdbx_struct_sheet_hbond / pdbx_validate_close_contact / pdbx_validate_symm_contact / struct_conf / struct_conn / struct_conn_type / struct_sheet / struct_sheet_order / struct_sheet_range / struct_site / struct_site_gen Item : _atom_site.B_iso_or_equiv / _atom_site.Cartn_x ... _atom_site.B_iso_or_equiv / _atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _atom_site.auth_seq_id / _pdbx_nonpoly_scheme.auth_seq_num / _pdbx_nonpoly_scheme.pdb_seq_num / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr2_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _pdbx_struct_sheet_hbond.range_1_auth_comp_id / _pdbx_struct_sheet_hbond.range_1_auth_seq_id / _pdbx_struct_sheet_hbond.range_1_label_comp_id / _pdbx_struct_sheet_hbond.range_1_label_seq_id / _pdbx_struct_sheet_hbond.range_2_auth_comp_id / _pdbx_struct_sheet_hbond.range_2_auth_seq_id / _pdbx_struct_sheet_hbond.range_2_label_comp_id / _pdbx_struct_sheet_hbond.range_2_label_seq_id / _pdbx_struct_sheet_hbond.sheet_id / _pdbx_validate_close_contact.auth_atom_id_1 / _pdbx_validate_close_contact.auth_atom_id_2 / _pdbx_validate_close_contact.auth_comp_id_1 / _pdbx_validate_close_contact.auth_comp_id_2 / _pdbx_validate_close_contact.auth_seq_id_1 / _pdbx_validate_close_contact.auth_seq_id_2 / _pdbx_validate_close_contact.dist / _pdbx_validate_symm_contact.auth_seq_id_1 / _pdbx_validate_symm_contact.auth_seq_id_2 / _pdbx_validate_symm_contact.dist / _struct_conf.pdbx_PDB_helix_id / _struct_sheet.id / _struct_sheet_order.sheet_id / _struct_sheet_range.sheet_id / _struct_site.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id / _struct_site_gen.auth_seq_id Revision 2.1 May 8, 2019 Group : Data collection / Experimental preparation / Category : exptl_crystal_grow / Item : _exptl_crystal_grow.methodRevision 2.2 May 1, 2024 Group : Data collection / Database references ... Data collection / Database references / Other / Refinement description Category : chem_comp_atom / chem_comp_bond ... chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model Item : _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf
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