4CQG

The crystal structure of MPK38 in complex with OTSSP167, an orally- administrative MELK selective inhibitor

4CQG の概要

• エントリーDOI: 10.2210/pdb4cqg/pdb
• 分子名称: Maternal embryonic leucine zipper kinase, 1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-({trans-4-[(dimethylamino)methyl]cyclohexyl}amino)-1,5-naphthyridin-3-yl]ethanone, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38909.86

構造登録者

Cho, Y.S.,Kang, Y.J.,Cho, H.S. (登録日: 2014-02-17, 公開日: 2014-07-09, 最終更新日: 2023-12-20)

主引用文献

Cho, Y.S.,Kang, Y.,Kim, K.,Cha, Y.J.,Cho, H.S.
The crystal structure of MPK38 in complex with OTSSP167, an orally administrative MELK selective inhibitor.
Biochem.Biophys.Res.Commun., 447:7-11, 2014

PubMed Abstract: Murine protein serine/threonine kinase 38 (MPK38), also known as maternal embryonic leucine zipper kinase (MELK), has been associated with various human cancers and plays an important role in the formation of cancer stem cells. OTSSP167, a MELK selective inhibitor, exhibits a strong in vitro activity, conferring an IC50 of 0.41nM and in vivo effect on various human cancer xenograft models. Here, we report the crystal structure of MPK38 (T167E), an active mutant, in complex with OTSSP167 and describe its detailed protein-inhibitor interactions. Comparison with the previous determined structure of MELK bound to the nanomolar inhibitors shows that OTSSP167 effectively fits into the active site, thus offering an opportunity for structure-based development and optimization of MELK inhibitors.

PubMed: 24657156
DOI: 10.1016/j.bbrc.2014.03.034

実験手法

X-RAY DIFFRACTION (2.57 Å)