Crystal Structure of Human Dual-Specificity Tyrosine-Regulated Kinase 3 Reveals New Structural Features and Insights into its Auto-phosphorylation

Kuglae Kim, Jeong Seok Cha, Yong Soon Cho, Hoyoung Kim, Nienping Chang, Hye Jung Kim, Hyun Soo Cho

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4 Citations (Scopus)


Dual-specificity tyrosine-regulated kinases (DYRKs) auto-phosphorylate a critical tyrosine residue in their activation loop and phosphorylate their substrate on serine and threonine residues. The auto-phosphorylation occurs intramolecularly and is a one-off event. DYRK3 is selectively expressed at a high level in hematopoietic cells and attenuates erythroblast development, leading to anemia. In the present study, we determined the crystal structure of the mature form of human DYRK3 in complex with harmine, an ATP competitive inhibitor. The crystal structure revealed a phosphorylation site, residue S350, whose phosphorylation increases the stability of DYRK3 and enhances its kinase activity. In addition, our structural and biochemical assays suggest that the N-terminal auto-phosphorylation accessory domain stabilizes the DYRK3 protein, followed by auto-phosphorylation of the tyrosine of the activation loop, which is important for kinase activity. Finally, our docking analysis provides information for the design of novel and potent therapeutics to treat anemia.

Original languageEnglish
Pages (from-to)1521-1530
Number of pages10
JournalJournal of Molecular Biology
Issue number10
Publication statusPublished - 2018 May 11


All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

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