4I5H

Crystal Structure of a Double Mutant Rat Erk2 Complexed With a Type II Quinazoline Inhibitor

4I5H の概要

• エントリーDOI: 10.2210/pdb4i5h/pdb
• 分子名称: Mitogen-activated protein kinase 1, N-{3-[2-(cyclopropylamino)quinazolin-6-yl]-4-methylphenyl}-3-(trifluoromethyl)benzamide (3 entities in total)
• 機能のキーワード: map kinase, dfg-out, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Rattus norvegicus (brown rat,rat,rats)
• 細胞内の位置: Cytoplasm, cytoskeleton, spindle (By similarity): P63086
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41815.97

構造登録者

Hari, S.B.,Maly, D.J.,Merritt, E.A. (登録日: 2012-11-28, 公開日: 2013-07-10, 最終更新日: 2024-02-28)

主引用文献

Hari, S.B.,Merritt, E.A.,Maly, D.J.
Sequence determinants of a specific inactive protein kinase conformation.
Chem.Biol., 20:806-815, 2013

PubMed Abstract: Only a small percentage of protein kinases have been shown to adopt a distinct inactive ATP-binding site conformation, called the Asp-Phe-Gly-out (DFG-out) conformation. Given the high degree of homology within this enzyme family, we sought to understand the basis of this disparity on a sequence level. We identified two residue positions that sensitize mitogen-activated protein kinases (MAPKs) to inhibitors that stabilize the DFG-out inactive conformation. After characterizing the structure and dynamics of an inhibitor-sensitive MAPK mutant, we demonstrated the generality of this strategy by sensitizing a kinase (apoptosis signal-regulating kinase 1) not in the MAPK family to several DFG-out stabilizing ligands, using the same residue positions. The use of specific inactive conformations may aid the study of noncatalytic roles of protein kinases, such as binding partner interactions and scaffolding effects.

PubMed: 23790491
DOI: 10.1016/j.chembiol.2013.05.005

実験手法

X-RAY DIFFRACTION (1.9 Å)