Entry Database : PDB / ID : 5ukl Structure visualization Downloads & linksTitle Human GRK2 in complex with Gbetagamma subunits and CCG222886 (14bd) Components(Guanine nucleotide-binding protein ...) x 2 Beta-adrenergic receptor kinase 1 G protein-coupled receptor kinase 2 DetailsKeywords TRANSFERASE/TRANSFERASE INHIBITOR / kinase / inhibitor complex / TRANSFERASE-TRANSFERASE INHIBITOR complexFunction / homology Function and homology informationFunction Domain/homology Component
beta-adrenergic-receptor kinase / negative regulation of the force of heart contraction by chemical signal / negative regulation of relaxation of smooth muscle / beta-adrenergic receptor kinase activity / G protein-coupled receptor kinase activity / Edg-2 lysophosphatidic acid receptor binding / alpha-2A adrenergic receptor binding / tachykinin receptor signaling pathway / positive regulation of catecholamine secretion / desensitization of G protein-coupled receptor signaling pathway ... beta-adrenergic-receptor kinase / negative regulation of the force of heart contraction by chemical signal / negative regulation of relaxation of smooth muscle / beta-adrenergic receptor kinase activity / G protein-coupled receptor kinase activity / Edg-2 lysophosphatidic acid receptor binding / alpha-2A adrenergic receptor binding / tachykinin receptor signaling pathway / positive regulation of catecholamine secretion / desensitization of G protein-coupled receptor signaling pathway / Activation of SMO / negative regulation of striated muscle contraction / regulation of the force of heart contraction / Calmodulin induced events / cardiac muscle contraction / regulation of signal transduction / Olfactory Signaling Pathway / Thromboxane signalling through TP receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Activation of the phototransduction cascade / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G protein-coupled acetylcholine receptor signaling pathway / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon signaling in metabolic regulation / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / viral genome replication / Vasopressin regulates renal water homeostasis via Aquaporins / photoreceptor disc membrane / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / sensory perception of taste / cellular response to catecholamine stimulus / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / ADP signalling through P2Y purinoceptor 1 / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / GPER1 signaling / heterotrimeric G-protein complex / Inactivation, recovery and regulation of the phototransduction cascade / G alpha (12/13) signalling events / cilium / signaling receptor complex adaptor activity / extracellular vesicle / ADORA2B mediated anti-inflammatory cytokines production / receptor internalization / Thrombin signalling through proteinase activated receptors (PARs) / phospholipase C-activating G protein-coupled receptor signaling pathway / presynapse / GTPase binding / Ca2+ pathway / G protein-coupled receptor binding / retina development in camera-type eye / G alpha (i) signalling events / Cargo recognition for clathrin-mediated endocytosis / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / peptidyl-threonine phosphorylation / postsynapse / cell population proliferation / heart development / Ras protein signal transduction / Extra-nuclear estrogen signaling / lysosomal membrane / G protein-coupled receptor signaling pathway / peptidyl-serine phosphorylation / protein kinase activity / GTPase activity / synapse / protein-containing complex binding / viral entry into host cell / protein phosphorylation / signal transduction / extracellular exosome / ATP binding / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function Helix Hairpins - #1270 / GPCR kinase / Transducin (heterotrimeric G protein), gamma chain / G Protein Gi Gamma 2 / Regulator of G-protein Signalling 4, domain 2 / Regulator of G-protein Signalling 4; domain 2 / Regulator of G protein signaling domain / RGS, subdomain 2 / RGS domain / RGS domain profile. ... Helix Hairpins - #1270 / GPCR kinase / Transducin (heterotrimeric G protein), gamma chain / G Protein Gi Gamma 2 / Regulator of G-protein Signalling 4, domain 2 / Regulator of G-protein Signalling 4; domain 2 / Regulator of G protein signaling domain / RGS, subdomain 2 / RGS domain / RGS domain profile. / Regulator of G protein signalling domain / RGS domain superfamily / Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB) / PH-domain like / YVTN repeat-like/Quinoprotein amine dehydrogenase / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. / PH domain / 7 Propeller / Methylamine Dehydrogenase; Chain H / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain superfamily / G-protein gamma-like domain / GGL domain / G protein gamma subunit-like motifs / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / PH domain profile. / Pleckstrin homology domain. / Pleckstrin homology domain / Few Secondary Structures / Irregular / G-protein beta WD-40 repeat / Helix Hairpins / PH-like domain superfamily / WD40 repeat, conserved site / Trp-Asp (WD) repeats circular profile. / Trp-Asp (WD) repeats signature. / WD domain, G-beta repeat / Trp-Asp (WD) repeats profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / Roll / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Protein kinase domain / Phosphorylase Kinase; domain 1 / 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 Beta / Mainly Alpha / Alpha Beta Similarity search - Domain/homology Chem-SIX / Beta-adrenergic receptor kinase 1 / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 Similarity search - ComponentBiological species Homo sapiens (human)Method X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution : 2.15 Å DetailsAuthors Cato, M.C. / Homan, K.T. / Tesmer, J.J.G. Funding support United States, 12items Details Hide detailsOrganization Grant number Country National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) HL071818 United States National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) HL086865 United States National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) HL122416 United States American Heart Association N014938 United States American Heart Association 15PRE22730028 United States National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) R37 HL061690 United States National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) P01 HL075443 United States National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) P01 HL108806 United States National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) P01 HL091799 United States Center for Discovery of New Medicine, University of Michigan United States National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) 5T32GM008597 United States Michigan Economic Development Corporation and Michigan Technology Tri-Corridor Grant 085P1000817 United States
CitationJournal : J. Med. Chem. / Year : 2017Title : Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors Based on Paroxetine.Authors : Waldschmidt, H.V. / Homan, K.T. / Cato, M.C. / Cruz-Rodriguez, O. / Cannavo, A. / Wilson, M.W. / Song, J. / Cheung, J.Y. / Koch, W.J. / Tesmer, J.J. / Larsen, S.D. History Deposition Jan 23, 2017 Deposition site : RCSB / Processing site : RCSBRevision 1.0 Apr 5, 2017 Provider : repository / Type : Initial releaseRevision 1.1 Apr 26, 2017 Group : Database referencesRevision 1.2 Sep 13, 2017 Group : Author supporting evidence / Category : pdbx_audit_support / Item : _pdbx_audit_support.funding_organizationRevision 1.3 Sep 27, 2017 Group : Data collection / Refinement description / Category : diffrn_detector / software / Item : _diffrn_detector.detectorRevision 1.4 Dec 4, 2019 Group : Author supporting evidence / Derived calculations / Category : pdbx_audit_support / pdbx_struct_special_symmetry / Item : _pdbx_audit_support.funding_organization
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