6C2Y

Human GRK2 in complex with Gbetagamma subunits and CCG257142

6C2Y の概要

• エントリーDOI: 10.2210/pdb6c2y/pdb
• 分子名称: 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)
• 機能のキーワード: transferase-signaling protein complex, transferase/signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 126304.04

構造登録者

Bouley, R.,Tesmer, J.J.G. (登録日: 2018-01-09, 公開日: 2018-04-25, 最終更新日: 2023-10-04)

主引用文献

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

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: 29627263
DOI: 10.1016/j.bmcl.2018.03.082

実験手法

X-RAY DIFFRACTION (2.74 Å)