Identification of a novel target site for ATP-independent ERK2 inhibitors

被引：5

作者：

Yoshida, Mayu ^{[1
]}

Nagao, Haruna ^{[2
]}

Sugiyama, Hajime ^{[3
]}

Sawa, Masaaki ^{[2
]}

Kinoshita, Takayoshi ^{[1
]}

机构：

[1] Osaka Prefecture Univ, Grad Sch Sci, Osaka 5998531, Japan

[2] Carna Biosci Inc, Kobe, Hyogo 6500047, Japan

[3] Mitsubishi Chem Corp, Yokohama, Kanagawa 2278502, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2022年 / 593卷

关键词：

ERK2; X-ray crystal structure; ATP-independent inhibitor; Molecular dynamics simulation; Activation loop; Cancer; ACTIVATION; KINASES; PATHWAY;

D O I：

10.1016/j.bbrc.2022.01.035

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：73 / 78

页数：6

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