7W41

Crystal Structure of Human Gastrin Releasing Peptide Receptor in complex with the antagonist PD176252

7W41 の概要

• エントリーDOI: 10.2210/pdb7w41/pdb
• 分子名称: Gastrin-releasing peptide receptor,GlgA glycogen synthase, (2S)-3-(1H-indol-3-yl)-N-[[1-(5-methoxypyridin-2-yl)cyclohexyl]methyl]-2-methyl-2-[(4-nitrophenyl)carbamoylamino]propanamide (2 entities in total)
• 機能のキーワード: gpcr, gastrin releasing peptide receptor, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 54959.42

構造登録者

Peng, S.,Zhan, Y.,Zhang, H. (登録日: 2021-11-26, 公開日: 2023-02-22, 最終更新日: 2024-10-16)

主引用文献

Peng, S.,Zhan, Y.,Zhang, D.,Ren, L.,Chen, A.,Chen, Z.F.,Zhang, H.
Structures of human gastrin-releasing peptide receptors bound to antagonist and agonist for cancer and itch therapy.
Proc.Natl.Acad.Sci.USA, 120:e2216230120-e2216230120, 2023

PubMed Abstract: Gastrin releasing peptide receptor (GRPR), a member of the bombesin (BBN) G protein-coupled receptors, is aberrantly overexpressed in several malignant tumors, including those of the breast, prostate, pancreas, lung, and central nervous system. Additionally, it also mediates non-histaminergic itch and pathological itch conditions in mice. Thus, GRPR could be an attractive target for cancer and itch therapy. Here, we report the inactive state crystal structure of human GRPR in complex with the non-peptide antagonist PD176252, as well as two active state cryo-electron microscopy (cryo-EM) structures of GRPR bound to the endogenous peptide agonist gastrin-releasing peptide and the synthetic BBN analog [D-Phe, β-Ala, Phe, Nle] Bn (6-14), in complex with G heterotrimers. These structures revealed the molecular mechanisms for the ligand binding, receptor activation, and G proteins signaling of GRPR, which are expected to accelerate the structure-based design of GRPR antagonists and agonists for the treatments of cancer and pruritus.

PubMed: 36724251
DOI: 10.1073/pnas.2216230120

実験手法

X-RAY DIFFRACTION (2.952 Å)