Entry Database : PDB / ID : 4pl4 Structure visualization Downloads & linksTitle Crystal structure of murine IRE1 in complex with OICR464 inhibitor ComponentsSerine/threonine-protein kinase/endoribonuclease IRE1 Details Keywords TRANSFERASE / HYDROLASE/INHIBITOR / Schiff base / hydroxy aryl aldehydes (HAA) / inhibitor complex / unfolded protein response / endoribonuclease / HYDROLASE-INHIBITOR complexFunction / homology Function and homology informationFunction Domain/homology Component
IRE1alpha activates chaperones / mRNA splicing, via endonucleolytic cleavage and ligation / AIP1-IRE1 complex / IRE1-TRAF2-ASK1 complex / positive regulation of ERAD pathway / insulin metabolic process / IRE1-RACK1-PP2A complex / platelet-derived growth factor receptor binding / Hydrolases; Acting on ester bonds; Endoribonucleases producing 5'-phosphomonoesters / positive regulation of endoplasmic reticulum unfolded protein response ... IRE1alpha activates chaperones / mRNA splicing, via endonucleolytic cleavage and ligation / AIP1-IRE1 complex / IRE1-TRAF2-ASK1 complex / positive regulation of ERAD pathway / insulin metabolic process / IRE1-RACK1-PP2A complex / platelet-derived growth factor receptor binding / Hydrolases; Acting on ester bonds; Endoribonucleases producing 5'-phosphomonoesters / positive regulation of endoplasmic reticulum unfolded protein response / endothelial cell proliferation / nuclear inner membrane / IRE1-mediated unfolded protein response / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / cellular response to vascular endothelial growth factor stimulus / endoplasmic reticulum unfolded protein response / positive regulation of JUN kinase activity / positive regulation of vascular associated smooth muscle cell proliferation / RNA endonuclease activity / Hsp70 protein binding / positive regulation of RNA splicing / cellular response to glucose stimulus / Hsp90 protein binding / ADP binding / cellular response to hydrogen peroxide / unfolded protein binding / endonuclease activity / protein autophosphorylation / non-specific serine/threonine protein kinase / negative regulation of translation / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / endoplasmic reticulum membrane / enzyme binding / magnesium ion binding / protein homodimerization activity / mitochondrion / ATP binding Similarity search - Function KEN domain / Serine/threonine-protein kinase/endoribonuclease IRE1/2-like / KEN domain / KEN domain superfamily / Ribonuclease 2-5A / KEN domain profile. / domain in protein kinases, N-glycanases and other nuclear proteins / de novo design (two linked rop proteins) / Pyrrolo-quinoline quinone beta-propeller repeat / beta-propeller repeat ... KEN domain / Serine/threonine-protein kinase/endoribonuclease IRE1/2-like / KEN domain / KEN domain superfamily / Ribonuclease 2-5A / KEN domain profile. / domain in protein kinases, N-glycanases and other nuclear proteins / de novo design (two linked rop proteins) / Pyrrolo-quinoline quinone beta-propeller repeat / beta-propeller repeat / Quinoprotein alcohol dehydrogenase-like superfamily / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / WD40/YVTN repeat-like-containing domain superfamily / Serine/Threonine protein kinases, catalytic domain / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / Up-down Bundle / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta Similarity search - Domain/homologyBiological species Mus musculus (house mouse)Method X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution : 3 Å DetailsAuthors Sanches, M. / Duffy, N. / Talukdar, M. / Thevakumaran, N. / Chiovitti, D. / Al-awar, R. / Patterson, J.B. / Sicheri, F. Funding support Canada, United States, 3items Details Hide detailsOrganization Grant number Country Canadian Institutes of Health Research (CIHR) MOP 84370 Canada Multiple Myeloma Research Foundation Biotech Investment Award United States Canadian Cancer Society Canada
CitationJournal : Nat Commun / Year : 2014Title : Structure and mechanism of action of the hydroxy-aryl-aldehyde class of IRE1 endoribonuclease inhibitors.Authors: Sanches, M. / Duffy, N.M. / Talukdar, M. / Thevakumaran, N. / Chiovitti, D. / Canny, M.D. / Lee, K. / Kurinov, I. / Uehling, D. / Al-Awar, R. / Poda, G. / Prakesch, M. / Wilson, B. / Tam, V. ... Authors : Sanches, M. / Duffy, N.M. / Talukdar, M. / Thevakumaran, N. / Chiovitti, D. / Canny, M.D. / Lee, K. / Kurinov, I. / Uehling, D. / Al-Awar, R. / Poda, G. / Prakesch, M. / Wilson, B. / Tam, V. / Schweitzer, C. / Toro, A. / Lucas, J.L. / Vuga, D. / Lehmann, L. / Durocher, D. / Zeng, Q. / Patterson, J.B. / Sicheri, F. History Deposition May 16, 2014 Deposition site : RCSB / Processing site : RCSBRevision 1.0 Sep 3, 2014 Provider : repository / Type : Initial releaseRevision 1.1 Sep 10, 2014 Group : Database referencesRevision 1.2 Nov 22, 2017 Group : Derived calculations / Other ... Derived calculations / Other / Refinement description / Source and taxonomy / Structure summary Category : entity_src_gen / pdbx_database_status ... entity_src_gen / pdbx_database_status / pdbx_struct_assembly / pdbx_struct_assembly_gen / pdbx_struct_conn_angle / pdbx_struct_oper_list / software / struct_keywords Item : _entity_src_gen.pdbx_alt_source_flag / _pdbx_database_status.pdb_format_compatible ... _entity_src_gen.pdbx_alt_source_flag / _pdbx_database_status.pdb_format_compatible / _pdbx_struct_assembly.oligomeric_details / _pdbx_struct_assembly_gen.asym_id_list / _pdbx_struct_oper_list.symmetry_operation / _software.classification / _struct_keywords.text Revision 1.3 Jan 8, 2020 Group : Author supporting evidence / Category : pdbx_audit_support / Item : _pdbx_audit_support.funding_organizationRevision 1.4 Sep 27, 2023 Group : Data collection / Database references ... Data collection / Database references / Derived calculations / Refinement description Category : chem_comp_atom / chem_comp_bond ... chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / refine_hist / struct_conn / struct_conn_type Item : _database_2.pdbx_DOI / _database_2.pdbx_database_accession ... _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _refine_hist.pdbx_number_atoms_nucleic_acid / _refine_hist.pdbx_number_atoms_protein / _struct_conn.conn_type_id / _struct_conn.id / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn_type.id
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