Entry Database : PDB / ID : 7mlk Structure visualization Downloads & linksTitle Crystal structure of human PI3Ka (p110a subunit) with MMV085400 bound to the active site determined at 2.9 angstroms resolution ComponentsPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Details Keywords TRANSFERASE/INHIBITOR / PI3K / pyrazine / complex / TRANSFERASE-INHIBITOR complexFunction / homology Function and homology informationFunction Domain/homology Component
response to muscle inactivity / negative regulation of actin filament depolymerization / response to L-leucine / regulation of actin filament organization / response to butyrate / IRS-mediated signalling / cellular response to hydrostatic pressure / autosome genomic imprinting / PI3K events in ERBB4 signaling / Activated NTRK2 signals through PI3K ... response to muscle inactivity / negative regulation of actin filament depolymerization / response to L-leucine / regulation of actin filament organization / response to butyrate / IRS-mediated signalling / cellular response to hydrostatic pressure / autosome genomic imprinting / PI3K events in ERBB4 signaling / Activated NTRK2 signals through PI3K / positive regulation of protein localization to membrane / Activated NTRK3 signals through PI3K / negative regulation of fibroblast apoptotic process / phosphatidylinositol 3-kinase complex, class IB / vasculature development / regulation of cellular respiration / Signaling by cytosolic FGFR1 fusion mutants / cardiac muscle cell contraction / phosphatidylinositol 3-kinase complex, class IA / phosphatidylinositol 3-kinase complex / Nephrin family interactions / anoikis / relaxation of cardiac muscle / Signaling by LTK in cancer / Costimulation by the CD28 family / 1-phosphatidylinositol-4-phosphate 3-kinase activity / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / Signaling by LTK / MET activates PI3K/AKT signaling / phosphatidylinositol-4,5-bisphosphate 3-kinase / PI3K/AKT activation / phosphatidylinositol 3-kinase / vascular endothelial growth factor signaling pathway / phosphatidylinositol-3-phosphate biosynthetic process / 1-phosphatidylinositol-3-kinase activity / Signaling by ALK / negative regulation of macroautophagy / PI-3K cascade:FGFR2 / PI-3K cascade:FGFR3 / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / protein kinase activator activity / PI-3K cascade:FGFR4 / response to dexamethasone / PI-3K cascade:FGFR1 / phosphatidylinositol-mediated signaling / Synthesis of PIPs at the plasma membrane / CD28 dependent PI3K/Akt signaling / phosphatidylinositol phosphate biosynthetic process / PI3K events in ERBB2 signaling / PI3K Cascade / negative regulation of anoikis / intercalated disc / RET signaling / insulin receptor substrate binding / Interleukin-3, Interleukin-5 and GM-CSF signaling / regulation of multicellular organism growth / positive regulation of TOR signaling / endothelial cell migration / RAC2 GTPase cycle / GAB1 signalosome / Role of phospholipids in phagocytosis / Role of LAT2/NTAL/LAB on calcium mobilization / adipose tissue development / Interleukin receptor SHC signaling / positive regulation of lamellipodium assembly / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / phagocytosis / Signaling by FGFR4 in disease / phosphorylation / cardiac muscle contraction / energy homeostasis / Signaling by FLT3 ITD and TKD mutants / Signaling by FGFR2 in disease / Signaling by FGFR3 in disease / Tie2 Signaling / GPVI-mediated activation cascade / T cell costimulation / FLT3 Signaling / response to muscle stretch / Signaling by FLT3 fusion proteins / RAC1 GTPase cycle / Signaling by FGFR1 in disease / phosphatidylinositol 3-kinase/protein kinase B signal transduction / Downstream signal transduction / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / liver development / insulin-like growth factor receptor signaling pathway / response to activity / Regulation of signaling by CBL / cellular response to glucose stimulus / positive regulation of smooth muscle cell proliferation / regulation of protein phosphorylation / Constitutive Signaling by EGFRvIII / Signaling by ERBB2 ECD mutants / Signaling by SCF-KIT / epidermal growth factor receptor signaling pathway / Signaling by ERBB2 KD Mutants / platelet activation / VEGFA-VEGFR2 Pathway Similarity search - Function PI3Kalpha, catalytic domain / PI3-kinase family, p85-binding domain / PI3-kinase family, p85-binding domain / 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 / Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain profile. / PI3-kinase family, ras-binding domain / C2 phosphatidylinositol 3-kinase-type domain ... PI3Kalpha, catalytic domain / PI3-kinase family, p85-binding domain / PI3-kinase family, p85-binding domain / 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 / Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain profile. / PI3-kinase family, ras-binding domain / C2 phosphatidylinositol 3-kinase-type domain / C2 phosphatidylinositol 3-kinase (PI3K)-type domain profile. / Phosphoinositide 3-kinase, region postulated to contain C2 domain / Phosphoinositide 3-kinase family, accessory domain (PIK domain) / Phosphoinositide 3-kinase C2 / Phosphoinositide 3-kinase, accessory (PIK) domain superfamily / Phosphoinositide 3-kinase family, accessory domain (PIK domain) / Phosphoinositide 3-kinase, accessory (PIK) domain / Phosphatidylinositol kinase / PIK helical domain profile. / Phosphatidylinositol 3- and 4-kinases signature 1. / Phosphatidylinositol 3- and 4-kinases signature 2. / Phosphatidylinositol 3/4-kinase, conserved site / Phosphatidylinositol 3-/4-kinase, catalytic domain superfamily / Phosphoinositide 3-kinase, catalytic domain / Phosphatidylinositol 3- and 4-kinases catalytic domain profile. / Phosphatidylinositol 3-/4-kinase, catalytic domain / Phosphatidylinositol 3- and 4-kinase / C2 domain superfamily / Armadillo-type fold / Ubiquitin-like domain superfamily / Protein kinase-like domain superfamily Similarity search - Domain/homologyBiological species Homo sapiens (human)Method X-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution : 2.91 Å DetailsAuthors Krake, S.H. / Martinez, P.D.G. / Poggi, M.L. / Ferreira, M.S. / Aguiar, A.C.C. / Souza, G.E. / Wenlock, M. / Jones, B. / Steinbrecher, T. / Day, T. ...Krake, S.H. / Martinez, P.D.G. / Poggi, M.L. / Ferreira, M.S. / Aguiar, A.C.C. / Souza, G.E. / Wenlock, M. / Jones, B. / Steinbrecher, T. / Day, T. / McPhail, J. / Burke, J. / Yeo, T. / Mok, S. / Uhlemann, A.C. / Fidock, D.A. / Chen, P. / Grodsky, N. / Deng, Y.L. / Guido, R.V.C. / Campbell, S.F. / Willis, P.A. / Dias, L.C. Funding support Brazil, 1items Details Hide detailsOrganization Grant number Country Other private RD-12-0103 Brazil
CitationJournal : To Be Published Title : Discovery of 2,6-disubstituted pyrazines as potent PI4K inhibitors with antimalarial activityAuthors: Krake, S.H. / Martinez, P.D.G. / Poggi, M.L. / Ferreira, M.S. / Aguiar, A.C.C. / Souza, G.E. / Wenlock, M. / Jones, B. / Steinbrecher, T. / Day, T. / McPhail, J. / Burke, J. / Yeo, T. / Mok, ... Authors : Krake, S.H. / Martinez, P.D.G. / Poggi, M.L. / Ferreira, M.S. / Aguiar, A.C.C. / Souza, G.E. / Wenlock, M. / Jones, B. / Steinbrecher, T. / Day, T. / McPhail, J. / Burke, J. / Yeo, T. / Mok, S. / Uhlemann, A.C. / Fidock, D.A. / Chen, P. / Grodsky, N. / Deng, Y.L. / Guido, R.V.C. / Campbell, S.F. / Willis, P.A. / Dias, L.C. History Deposition Apr 28, 2021 Deposition site : RCSB / Processing site : RCSBRevision 1.0 May 4, 2022 Provider : repository / Type : Initial releaseRevision 1.1 Oct 18, 2023 Group : Data collection / Refinement descriptionCategory : chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
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