6c2y

Human GRK2 in complex with Gbetagamma subunits and CCG257142

spinqualitylabelsall models 6c2y, resolution 2.74Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6c2y is a 3 chain structure with sequence from Bovin and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EJS Gene: GRK2, ADRBK1, BARK, BARK1 (HUMAN), GNB1 (BOVIN), GNG2 (BOVIN) Activity: [Beta-adrenergic-receptor_kinase [Beta-adrenergic-receptor] kinase], with EC number 2.7.11.15 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ARBK1_HUMAN] Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them. Key regulator of LPAR1 signaling. Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor. Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner. [GBG2_BOVIN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. [GBB1_BOVIN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. Publication Abstract from PubMed G protein-coupled receptor (GPCR) kinases (GRKs) regulate the desensitization and internalization of GPCRs. Two of these, GRK2 and GRK5, are upregulated in heart failure and are promising targets for heart failure treatment. Although there have been several reports of potent and selective inhibitors of GRK2 there are few for GRK5. Herein, we describe a ligand docking approach utilizing the crystal structures of the GRK2-Gbetagamma.GSK180736A and GRK5.CCG215022 complexes to search for amide substituents predicted to confer GRK2 and/or GRK5 potency and selectivity. From this campaign, we successfully generated two new potent GRK5 inhibitors, although neither exhibited selectivity over GRK2. Utilizing a structure-based docking approach to develop potent G protein-coupled receptor kinase (GRK) 2 and 5 inhibitors.,Waldschmidt HV, Bouley R, Kirchhoff PD, Lee P, Tesmer JJG, Larsen SD Bioorg Med Chem Lett. 2018 May 15;28(9):1507-1515. doi:, 10.1016/j.bmcl.2018.03.082. Epub 2018 Mar 30. PMID:29627263 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta adrenergic receptor kinase 3D structures

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