Fig. 1: Structure of the human HIPK3 kinase domain.
From: Abemaciclib is a potent inhibitor of DYRK1A and HIP kinases involved in transcriptional regulation
a Phylogenetic tree of human HIPK1–4 and DYRK1A kinases illustrating the homology of the catalytic domains. The average distance tree was calculated by percentage identity using Jalview63. b Domain architecture of human HIPK1–4 and DYRK1A. HID homeoprotein-interacting domain, PEST proline, glutamate, serine, threonine-rich region, SQA serine, glutamine, alanine-rich region, DH DYRK homology box, HRD histidine-rich domain, ST serine/threonine-rich region. c Crystal structure of the human HIPK3 kinase domain (PDB: 7O7I). Key elements as the αC helix, the DFG motif, and the phosphorylated tyrosine within the activation loop are indicated. The CMGC insert region (residues 416–493) embedded between canonical helices αG and αH is colored from green to orange. d Coordination of the active center of the HIPK3 kinase. Electrostatic and hydrogen-bond interactions between the phosphorylated tyrosine of the activation loop, pY359, the RYYR element, the HAD motif with the general base, the DFG motif, the catalytic lysine K226 and the coordinating glutamate E241 of the αC helix are shown.
