1 research outputs found
Structural Insight into Maternal Embryonic Leucine Zipper Kinase (MELK) Conformation and Inhibition toward Structure-Based Drug Design
Maternal
embryonic leucine zipper kinase (MELK) is upregulated
in several types of tumor, including breast, prostate, and brain tumors.
Its expression is generally associated with cell survival, cell proliferation,
and resistance to apoptosis. Therefore, the potential of MELK inhibitors
as therapeutic agents is recently attracting considerable interest.
Here we report the first structures of MELK in complex with AMP–PNP
and with nanomolar inhibitors. Our studies shed light on the role
of the MELK UBA domain, provide a characterization of the kinase active
site, and identify key residues for achieving high potency, laying
the groundwork for structure-based drug design efforts