7W5O

Crystal structure of ERK2 with an allosteric inhibitor

7W5O の概要

• エントリーDOI: 10.2210/pdb7w5o/pdb
• 分子名称: Mitogen-activated protein kinase 1, (2R,3R,4S,5R)-2-(4-AMINO-5-IODO-7H-PYRROLO[2,3-D]PYRIMIDIN-7-YL)-5-(HYDROXYMETHYL)TETRAHYDROFURAN-3,4-DIOL, MALONIC ACID, ... (9 entities in total)
• 機能のキーワード: protein kinase, allosteric inhibitor, activation loop, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 87004.71

構造登録者

Yoshida, M.,Kinoshita, T. (登録日: 2021-11-30, 公開日: 2022-02-23, 最終更新日: 2023-11-29)

主引用文献

Yoshida, M.,Nagao, H.,Sugiyama, H.,Sawa, M.,Kinoshita, T.
Identification of a novel target site for ATP-independent ERK2 inhibitors.
Biochem.Biophys.Res.Commun., 593:73-78, 2022

PubMed Abstract: Extracellular signal-regulated kinase 2 (ERK2) controls vital physiological processes involving proliferation and differentiation and is a drug target molecule for many diseases such as cancers. In silico screening focusing on an allosteric site that plays a crucial role in substrate anchoring conferred an ERK2 inhibitor (compound 1). However, a competitive binding assay indicated that compound 1 did not bind to the allosteric site. Here, the crystal structure of ERK2 in complex with compound 1 revealed a novel binding site. This finding demonstrates the feasibility of developing new types of ERK2 inhibitors.

PubMed: 35063772
DOI: 10.1016/j.bbrc.2022.01.035

実験手法

X-RAY DIFFRACTION (2.35 Å)