Entry Database : PDB / ID : 8v8i Structure visualization Downloads & linksTitle PI3Ka H1047R co-crystal structure with inhibitor in cryptic pocket (compound 5). Components(Phosphatidylinositol ... ) x 2 Details Keywords SIGNALING PROTEIN / H1047R / PI3K / PI3KaFunction / homology Function and homology informationFunction Domain/homology Component
perinuclear endoplasmic reticulum membrane / response to muscle inactivity / negative regulation of actin filament depolymerization / regulation of toll-like receptor 4 signaling pathway / response to L-leucine / phosphatidylinositol kinase activity / regulation of actin filament organization / phosphatidylinositol 3-kinase regulator activity / response to butyrate / positive regulation of focal adhesion disassembly ... perinuclear endoplasmic reticulum membrane / response to muscle inactivity / negative regulation of actin filament depolymerization / regulation of toll-like receptor 4 signaling pathway / response to L-leucine / phosphatidylinositol kinase activity / regulation of actin filament organization / phosphatidylinositol 3-kinase regulator activity / response to butyrate / positive regulation of focal adhesion disassembly / autosome genomic imprinting / IRS-mediated signalling / cellular response to hydrostatic pressure / phosphatidylinositol 3-kinase activator activity / interleukin-18-mediated signaling pathway / PI3K events in ERBB4 signaling / myeloid leukocyte migration / 1-phosphatidylinositol-3-kinase regulator activity / phosphatidylinositol 3-kinase regulatory subunit binding / neurotrophin TRKA receptor binding / Activated NTRK2 signals through PI3K / positive regulation of protein localization to membrane / cis-Golgi network / Activated NTRK3 signals through PI3K / ErbB-3 class receptor binding / negative regulation of fibroblast apoptotic process / RHOF GTPase cycle / kinase activator activity / cardiac muscle cell contraction / phosphatidylinositol 3-kinase complex, class IB / vasculature development / transmembrane receptor protein tyrosine kinase adaptor activity / RHOD GTPase cycle / Signaling by cytosolic FGFR1 fusion mutants / regulation of cellular respiration / positive regulation of endoplasmic reticulum unfolded protein response / enzyme-substrate adaptor activity / phosphatidylinositol 3-kinase complex, class IA / anoikis / phosphatidylinositol 3-kinase complex / Nephrin family interactions / RND1 GTPase cycle / Costimulation by the CD28 family / relaxation of cardiac muscle / 1-phosphatidylinositol-4-phosphate 3-kinase activity / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / RND2 GTPase cycle / MET activates PI3K/AKT signaling / PI3K/AKT activation / RND3 GTPase cycle / positive regulation of leukocyte migration / positive regulation of filopodium assembly / phosphatidylinositol-4,5-bisphosphate 3-kinase / vascular endothelial growth factor signaling pathway / negative regulation of stress fiber assembly / phosphatidylinositol 3-kinase / growth hormone receptor signaling pathway / insulin binding / phosphatidylinositol-3-phosphate biosynthetic process / RHOV GTPase cycle / negative regulation of macroautophagy / 1-phosphatidylinositol-3-kinase activity / RHOB GTPase cycle / negative regulation of cell-matrix adhesion / Signaling by ALK / GP1b-IX-V activation signalling / PI-3K cascade:FGFR3 / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / protein kinase activator activity / response to dexamethasone / PI-3K cascade:FGFR2 / RHOJ GTPase cycle / PI-3K cascade:FGFR4 / RHOC GTPase cycle / PI-3K cascade:FGFR1 / negative regulation of osteoclast differentiation / intracellular glucose homeostasis / phosphatidylinositol-mediated signaling / phosphatidylinositol phosphate biosynthetic process / CD28 dependent PI3K/Akt signaling / Synthesis of PIPs at the plasma membrane / CDC42 GTPase cycle / RHOU GTPase cycle / PI3K events in ERBB2 signaling / negative regulation of anoikis / RHOG GTPase cycle / intercalated disc / T cell differentiation / RET signaling / regulation of multicellular organism growth / extrinsic apoptotic signaling pathway via death domain receptors / insulin receptor substrate binding / Interleukin-3, Interleukin-5 and GM-CSF signaling / PI3K Cascade / RHOA GTPase cycle / positive regulation of TOR signaling / endothelial cell migration / RAC2 GTPase cycle / RAC3 GTPase cycle / Role of phospholipids in phagocytosis Similarity search - Function PI3Kalpha, catalytic domain / Phosphatidylinositol 3-kinase regulatory subunit alpha, SH3 domain / PIK3R1, inter-SH2 domain / PI3K p85 subunit, C-terminal SH2 domain / PI3K regulatory subunit p85-related , inter-SH2 domain / PI3K p85 subunit, N-terminal SH2 domain / Phosphatidylinositol 3-kinase regulatory subunit P85 inter-SH2 domain / PI3-kinase family, p85-binding domain / PI3-kinase family, p85-binding domain / Rho GTPase-activating protein domain ... PI3Kalpha, catalytic domain / Phosphatidylinositol 3-kinase regulatory subunit alpha, SH3 domain / PIK3R1, inter-SH2 domain / PI3K p85 subunit, C-terminal SH2 domain / PI3K regulatory subunit p85-related , inter-SH2 domain / PI3K p85 subunit, N-terminal SH2 domain / Phosphatidylinositol 3-kinase regulatory subunit P85 inter-SH2 domain / PI3-kinase family, p85-binding domain / PI3-kinase family, p85-binding domain / Rho GTPase-activating protein domain / RhoGAP domain / Rho GTPase-activating proteins domain profile. / GTPase-activator protein for Rho-like GTPases / Phosphatidylinositol 3-kinase, adaptor-binding domain / Phosphatidylinositol 3-kinase adaptor-binding (PI3K ABD) domain profile. / PI3-kinase family, Ras-binding domain / Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain / PI3-kinase family, ras-binding domain / Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain profile. / Phosphoinositide 3-kinase C2 / Phosphoinositide 3-kinase, region postulated to contain C2 domain / C2 phosphatidylinositol 3-kinase-type domain / C2 phosphatidylinositol 3-kinase (PI3K)-type domain profile. / Phosphoinositide 3-kinase, accessory (PIK) domain superfamily / Phosphoinositide 3-kinase family, accessory domain (PIK domain) / Phosphoinositide 3-kinase family, accessory domain (PIK domain) / Rho GTPase activation protein / Phosphoinositide 3-kinase, accessory (PIK) domain / Phosphatidylinositol kinase / PIK helical domain profile. / Phosphatidylinositol 3- and 4-kinases signature 1. / Phosphatidylinositol 3/4-kinase, conserved site / Phosphatidylinositol 3- and 4-kinases signature 2. / Phosphatidylinositol 3-/4-kinase, catalytic domain superfamily / Phosphoinositide 3-kinase, catalytic domain / Phosphatidylinositol 3- and 4-kinase / Phosphatidylinositol 3- and 4-kinases catalytic domain profile. / Phosphatidylinositol 3-/4-kinase, catalytic domain / C2 domain superfamily / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / Src homology 3 domains / SH2 domain superfamily / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain / Armadillo-type fold / Ubiquitin-like domain superfamily / Protein kinase-like domain superfamily Similarity search - Domain/homology : / : / Phosphatidylinositol 3-kinase regulatory subunit alpha / Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Similarity search - ComponentBiological species Homo sapiens (human)Method X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution : 3.2 Å DetailsAuthors Gunn, R.J. / Lawson, J.D. Funding support United States, 1items Details Hide detailsOrganization Grant number Country Not funded United States
CitationJournal : J.Med.Chem. / Year : 2024Title : Discovery of Pyridopyrimidinones that Selectively Inhibit the H1047R PI3K alpha Mutant Protein.Authors: Ketcham, J.M. / Harwood, S.J. / Aranda, R. / Aloiau, A.N. / Bobek, B.M. / Briere, D.M. / Burns, A.C. / Caddell Haatveit, K. / Calinisan, A. / Clarine, J. / Elliott, A. / Engstrom, L.D. / ... Authors : Ketcham, J.M. / Harwood, S.J. / Aranda, R. / Aloiau, A.N. / Bobek, B.M. / Briere, D.M. / Burns, A.C. / Caddell Haatveit, K. / Calinisan, A. / Clarine, J. / Elliott, A. / Engstrom, L.D. / Gunn, R.J. / Ivetac, A. / Jones, B. / Kuehler, J. / Lawson, J.D. / Nguyen, N. / Parker, C. / Pearson, K.E. / Rahbaek, L. / Saechao, B. / Wang, X. / Waters, A. / Waters, L. / Watkins, A.H. / Olson, P. / Smith, C.R. / Christensen, J.G. / Marx, M.A. History Deposition Dec 5, 2023 Deposition site : RCSB / Processing site : RCSBRevision 1.0 Mar 20, 2024 Provider : repository / Type : Initial releaseRevision 1.1 Mar 27, 2024 Group : Database references / Category : citation / citation_authorItem : _citation.pdbx_database_id_PubMed / _citation.title ... _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID / _citation_author.name Revision 1.2 Apr 10, 2024 Group : Database references / Category : citationItem : _citation.journal_volume / _citation.page_first / _citation.page_last
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