Characterization of Covalent Pyrazolopyrimidine-MKK7 Complexes and a Report on a Unique DFG-in/Leu-in Conformation of Mitogen-Activated Protein Kinase Kinase 7 (MKK7).,Journal of Medicinal Chemistry

当前位置： X-MOL 学术 › J. Med. Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Characterization of Covalent Pyrazolopyrimidine-MKK7 Complexes and a Report on a Unique DFG-in/Leu-in Conformation of Mitogen-Activated Protein Kinase Kinase 7 (MKK7).
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2019-05-31 , DOI: 10.1021/acs.jmedchem.9b00472
Patrik Wolle _{1,

2} , Julian Engel ₁ , Steven Smith ₁ , Lisa Goebel _{1,

2} , Elisabeth Hennes ₁ , Jonas Lategahn _{1,

2} , Daniel Rauh _{1,

2}

Affiliation

Pyrazolopyrimidines are well-established as covalent inhibitors of protein kinases such as the epidermal growth factor receptor or Bruton's tyrosine kinase, and we recently described their potential in targeting mitogen-activated protein kinase kinase 7 (MKK7). Herein, we report the structure-activity relationship of pyrazolopyrimidine-based MKK7 inhibitors and solved several complex crystal structures to gain insights into their binding mode. In addition, we present two structures of apo-MKK7, exhibiting a DFG-out and an unprecedented DFG-in/Leu-in conformation.

中文翻译：

共价吡唑并嘧啶-MKK7复合物的表征和丝裂素活化蛋白激酶激酶7（MKK7）独特DFG-in / Leu-in构象的报告。

吡唑并嘧啶已被广泛确立为蛋白激酶（例如表皮生长因子受体或Bruton酪氨酸激酶）的共价抑制剂，我们最近描述了它们靶向有丝分裂原激活的蛋白激酶7（MKK7）的潜力。在这里，我们报告了基于吡唑并嘧啶的MKK7抑制剂的结构活性关系，并解决了几种复杂的晶体结构，以了解其结合模式。另外，我们提出了载脂蛋白-MKK7的两个结构，展示了DFG-out和前所未有的DFG-in / Leu-in构象。

更新日期：2019-05-14

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南