Entry Database : PDB / ID : 8u37 Structure visualization Downloads & linksTitle Crystal structure of the catalytic domain of human PKC alpha (D463N, V568I, S657E) in complex with NVP-CJL037 at 2.48-A resolution ComponentsProtein kinase C alpha type Details Keywords TRANSFERASE/INHIBITOR / TRANSFERASE-INHIBITOR complexFunction / homology Function and homology informationFunction Domain/homology Component
Disinhibition of SNARE formation / Response to elevated platelet cytosolic Ca2+ / positive regulation of angiotensin-activated signaling pathway / desmosome assembly / positive regulation of dense core granule biogenesis / histone H3T6 kinase activity / calcium,diacylglycerol-dependent serine/threonine kinase activity / HuR (ELAVL1) binds and stabilizes mRNA / Depolymerization of the Nuclear Lamina / Trafficking of GluR2-containing AMPA receptors ... Disinhibition of SNARE formation / Response to elevated platelet cytosolic Ca2+ / positive regulation of angiotensin-activated signaling pathway / desmosome assembly / positive regulation of dense core granule biogenesis / histone H3T6 kinase activity / calcium,diacylglycerol-dependent serine/threonine kinase activity / HuR (ELAVL1) binds and stabilizes mRNA / Depolymerization of the Nuclear Lamina / Trafficking of GluR2-containing AMPA receptors / ROBO receptors bind AKAP5 / WNT5A-dependent internalization of FZD4 / Acetylcholine regulates insulin secretion / protein kinase C / negative regulation of glial cell apoptotic process / diacylglycerol-dependent serine/threonine kinase activity / mitotic nuclear membrane disassembly / regulation of platelet aggregation / positive regulation of macrophage differentiation / positive regulation of lipopolysaccharide-mediated signaling pathway / alphav-beta3 integrin-PKCalpha complex / Calmodulin induced events / Syndecan interactions / Regulation of KIT signaling / positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of cardiac muscle hypertrophy / positive regulation of cell adhesion / RET signaling / RHO GTPases Activate NADPH Oxidases / positive regulation of blood vessel endothelial cell migration / positive regulation of bone resorption / positive regulation of endothelial cell proliferation / regulation of mRNA stability / EGFR Transactivation by Gastrin / positive regulation of endothelial cell migration / SHC1 events in ERBB2 signaling / response to interleukin-1 / positive regulation of mitotic cell cycle / post-translational protein modification / ciliary basal body / VEGFR2 mediated cell proliferation / mitochondrial membrane / apoptotic signaling pathway / peptidyl-threonine phosphorylation / Signaling by SCF-KIT / G alpha (z) signalling events / positive regulation of angiogenesis / Inactivation, recovery and regulation of the phototransduction cascade / integrin binding / Ca2+ pathway / peptidyl-serine phosphorylation / angiogenesis / positive regulation of ERK1 and ERK2 cascade / cell adhesion / protein kinase activity / intracellular signal transduction / positive regulation of cell migration / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / perinuclear region of cytoplasm / enzyme binding / endoplasmic reticulum / mitochondrion / zinc ion binding / extracellular exosome / nucleoplasm / ATP binding / plasma membrane / cytoplasm / cytosol Similarity search - Function Classical Protein Kinase C alpha, catalytic domain / Protein kinase C, alpha/beta/gamma types / Protein kinase, C-terminal / Protein kinase C terminal domain / Diacylglycerol/phorbol-ester binding / Phorbol esters/diacylglycerol binding domain (C1 domain) / Zinc finger phorbol-ester/DAG-type signature. / C2 domain / Protein kinase C conserved region 2 (CalB) / Zinc finger phorbol-ester/DAG-type profile. ... Classical Protein Kinase C alpha, catalytic domain / Protein kinase C, alpha/beta/gamma types / Protein kinase, C-terminal / Protein kinase C terminal domain / Diacylglycerol/phorbol-ester binding / Phorbol esters/diacylglycerol binding domain (C1 domain) / Zinc finger phorbol-ester/DAG-type signature. / C2 domain / Protein kinase C conserved region 2 (CalB) / Zinc finger phorbol-ester/DAG-type profile. / Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains) / Protein kinase C-like, phorbol ester/diacylglycerol-binding domain / C2 domain / C2 domain profile. / C1-like domain superfamily / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. / C2 domain superfamily / 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 Similarity search - Domain/homologyBiological species Homo sapiens (human)Method X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution : 2.48 Å DetailsAuthors Romanowski, M.J. / Lam, J. / Visser, M. Funding support United States, 1items Details Hide detailsOrganization Grant number Country Other private United States
CitationJournal : J.Med.Chem. / Year : 2024Title : Discovery of Darovasertib (NVP-LXS196), a Pan-PKC Inhibitor for the Treatment of Metastatic Uveal Melanoma.Authors: Visser, M. / Papillon, J.P.N. / Luzzio, M. / LaMarche, M.J. / Fan, J. / Michael, W. / Wang, D. / Zhang, A. / Straub, C. / Mathieu, S. / Kato, M. / Palermo, M. / Chen, C. / Ramsey, T. / Joud, ... Authors : Visser, M. / Papillon, J.P.N. / Luzzio, M. / LaMarche, M.J. / Fan, J. / Michael, W. / Wang, D. / Zhang, A. / Straub, C. / Mathieu, S. / Kato, M. / Palermo, M. / Chen, C. / Ramsey, T. / Joud, C. / Barrett, R. / Vattay, A. / Guo, R. / Bric, A. / Chung, F. / Liang, G. / Romanowski, M.J. / Lam, J. / Thohan, S. / Atassi, F. / Wylie, A. / Cooke, V.G. History Deposition Sep 7, 2023 Deposition site : RCSB / Processing site : RCSBRevision 1.0 Jan 24, 2024 Provider : repository / Type : Initial releaseRevision 1.1 Jan 31, 2024 Group : Database references / Category : citationItem : _citation.journal_volume / _citation.page_first / _citation.page_last
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