6QHR

Structure of the mitogen activated kinase kinase 7 in complex with pyrazolopyrimidine 1m

6QHR の概要

• エントリーDOI: 10.2210/pdb6qhr/pdb
• 関連するPDBエントリー: 6QFL 6QFR 6QFT 6QG4 6QG7
• 分子名称: Dual specificity mitogen-activated protein kinase kinase 7, 1-[(3~{R})-3-[4-azanyl-3-(1~{H}-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]propan-1-one (3 entities in total)
• 機能のキーワード: protein kinase, kinase, mkk7, transferase
• 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: 36537.30

構造登録者

Wolle, P.,Mueller, M.P.,Rauh, D. (登録日: 2019-01-17, 公開日: 2019-05-22, 最終更新日: 2024-11-06)

主引用文献

Wolle, P.,Engel, J.,Smith, S.,Goebel, L.,Hennes, E.,Lategahn, J.,Rauh, D.
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).
J.Med.Chem., 62:5541-5546, 2019

PubMed Abstract: 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.

PubMed: 31083997
DOI: 10.1021/acs.jmedchem.9b00472

実験手法

X-RAY DIFFRACTION (2.52 Å)