6QFT

Structure of the mitogen activated kinase kinase 7 in complex with pyrazolopyrimidin 1b

6QFT の概要

• エントリーDOI: 10.2210/pdb6qft/pdb
• 関連するPDBエントリー: 6QFL 6QFR
• 分子名称: Dual specificity mitogen-activated protein kinase kinase 7, 1-[(3~{R})-3-(4-azanyl-3-iodanyl-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: 36547.08

構造登録者

Wolle, P.,Mueller, M.P.,Rauh, D. (登録日: 2019-01-10, 公開日: 2019-05-22, 最終更新日: 2024-11-13)

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 (2.7 Å)