4N4S

A Double Mutant Rat Erk2 in Complex With a Pyrazolo[3,4-d]pyrimidine Inhibitor

4N4S の概要

• エントリーDOI: 10.2210/pdb4n4s/pdb
• 分子名称: Mitogen-activated protein kinase 1, 3-[2-(benzyloxy)-8-methylquinolin-6-yl]-1-(propan-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (3 entities in total)
• 機能のキーワード: serine/threonine kinase, map kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Rattus norvegicus (rat)
• 細胞内の位置: Cytoplasm, cytoskeleton, spindle (By similarity): P63086
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 83556.00

構造登録者

Hari, S.B.,Maly, D.J.,Merritt, E.A. (登録日: 2013-10-08, 公開日: 2014-04-16, 最終更新日: 2023-09-20)

主引用文献

Hari, S.B.,Merritt, E.A.,Maly, D.J.
Conformation-Selective ATP-Competitive Inhibitors Control Regulatory Interactions and Noncatalytic Functions of Mitogen-Activated Protein Kinases.
Chem.Biol., 21:628-635, 2014

PubMed Abstract: Most potent protein kinase inhibitors act by competing with ATP to block the phosphotransferase activity of their targets. However, emerging evidence demonstrates that ATP-competitive inhibitors can affect kinase interactions and functions in ways beyond blocking catalytic activity. Here, we show that stabilizing alternative ATP-binding site conformations of the mitogen-activated protein kinases (MAPKs) p38α and Erk2 with ATP-competitive inhibitors differentially, and in some cases divergently, modulates the abilities of these kinases to interact with upstream activators and deactivating phosphatases. Conformation-selective ligands are also able to modulate Erk2's ability to allosterically activate the MAPK phosphatase DUSP6, highlighting how ATP-competitive ligands can control noncatalytic kinase functions. Overall, these studies underscore the relationship between the ATP-binding and regulatory sites of MAPKs and provide insight into how ATP-competitive ligands can be designed to confer graded control over protein kinase function.

PubMed: 24704509
DOI: 10.1016/j.chembiol.2014.02.016

実験手法

X-RAY DIFFRACTION (2.2 Å)