6C2Y
Human GRK2 in complex with Gbetagamma subunits and CCG257142
Summary for 6C2Y
| Entry DOI | 10.2210/pdb6c2y/pdb |
| Descriptor | Beta-adrenergic receptor kinase 1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (5 entities in total) |
| Functional Keywords | transferase-signaling protein complex, transferase/signaling protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 126304.04 |
| Authors | Bouley, R.,Tesmer, J.J.G. (deposition date: 2018-01-09, release date: 2018-04-25, Last modification date: 2023-10-04) |
| Primary citation | Waldschmidt, H.V.,Bouley, R.,Kirchhoff, P.D.,Lee, P.,Tesmer, J.J.G.,Larsen, S.D. Utilizing a structure-based docking approach to develop potent G protein-coupled receptor kinase (GRK) 2 and 5 inhibitors. Bioorg. Med. Chem. Lett., 28:1507-1515, 2018 Cited by PubMed Abstract: 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-Gβγ·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. PubMed: 29627263DOI: 10.1016/j.bmcl.2018.03.082 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.74 Å) |
Structure validation
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