PDBsum entry 4bky

Transferase

PDB id: 4bky

Contents

Protein chain

311 a.a.

Ligands

82B

UNX

Waters ×159

References listed in PDB file

Key reference

• Title: Structural insight into maternal embryonic leucine zipper kinase (melk) conformation and inhibition toward structure-Based drug design.
• Authors: G.Canevari, S.Re depaolini, U.Cucchi, J.A.Bertrand, E.Casale, C.Perrera, B.Forte, P.Carpinelli, E.R.Felder.
• Ref.: Biochemistry, 2013, 52, 6380-6387. [DOI no: 10.1021/bi4005864]
• PubMed id: 23914841

Abstract

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.