9BRI

Crystal Structure of Human G Protein-Coupled Receptor Kinase 5 in Complex with GRL064-22

これはPDB形式変換不可エントリーです。

9BRI の概要

• エントリーDOI: 10.2210/pdb9bri/pdb
• 分子名称: G protein-coupled receptor kinase 5, (3Z)-3-[(3,5-dimethyl-4-{[(2S)-5-oxooxolane-2-carbonyl]amino}-1H-pyrrol-2-yl)methylidene]-N-[(1R)-1-(4-fluorophenyl)ethyl]-2-oxo-2,3-dihydro-1H-indole-5-carboxamide (3 entities in total)
• 機能のキーワード: g protein-coupled receptor, gpcr g protein-coupled receptor kinase, grk kinase, signaling protein-inhibitor complex, signaling protein/inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 69462.27

構造登録者

Chen, Y.,Tesmer, J.J.G. (登録日: 2024-05-11, 公開日: 2025-02-19)

主引用文献

Ghosh, A.K.,Chen, Y.,Gadi, R.K.,Sonawane, A.,Gamage, S.P.,Tesmer, J.G.
Design, synthesis, and X-ray structural studies of a series of highly potent, selective, and drug-like G protein-coupled receptor kinase 5 inhibitors.
Eur.J.Med.Chem., 282:117024-117024, 2025

PubMed Abstract: G protein-coupled receptor kinase 5 (GRK5) has emerged as a potential drug development target against heart failure and cancer. A close homolog, GRK6 represents a therapeutic target for multiple myeloma. We have rationally designed a series of highly selective, potent, noncovalent, and drug-like GRK5 inhibitors. Several inhibitors exhibited low nanomolar GRK5 inhibition and high selectivity over GRK2, and, surprisingly, some were selective for GRK6. We determined high-resolution X-ray crystal structures of several inhibitors in complex with GRK5, which provide molecular insights into the ligand-binding site interactions responsible for GRK5 selectivity and potency.

PubMed: 39549325
DOI: 10.1016/j.ejmech.2024.117024

実験手法

X-RAY DIFFRACTION (2.9 Å)