Summary
PDB 4BKZ deposited: 2013-04-30 modified: 2013-10-02
Title Crystal structure of unphosphorylated Maternal Embryonic Leucine zipper Kinase (MELK) in complex with a benzodipyrazole inhibitor
Authors Bertrand, J.A., Canevari, G., Carpinelli, P., Casale, E., Cucchi, U., Felder, E.R., Forte, B., Perrera, C., Re Depaolini, S.
Method X-RAY DIFFRACTION
Structure factors resolution 2.2 rfactor 0.19854 rfree 0.24023
DPI 0.56 theoretical min: 0.24
Related PDB Entries 4BKY
Citations

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.

Biochemistry 2013 Sep; 52(37):6380- doi:10.1021/BI4005864

Cross References
Database source Identifier Description
PubMed 23914841 BICHAW
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
4BKZ/0 4BKZ 0 monomer 0 1 1 2295