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

Yong Soon Cho, Yingjin Kang, Kuglae Kim, Young Je Cha, Hyun Soo Cho

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

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 0.41 nM 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.

Original languageEnglish
Pages (from-to)7-11
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume447
Issue number1
DOIs
Publication statusPublished - 2014 Apr 25

Bibliographical note

Funding Information:
We are grateful to the staff scientists at the BL-17A beamline of the Photon Factory and the 5A beamline of the Pohang Light Source for data collection. This work was supported by the Mid-career Researcher Program through a NRF grant funded by the Korea government (MEST) (Nos. 2009-0073145 , 2009-0084897 , NRF-2012R1A2A2A01012830 ) and by a grant of the Korea Healthcare Technology R&D project , Ministry for Health, Welfare & Family Affairs , the Republic of Korea ( A080320 ).

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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