Structural analysis of the polo‐box domain of human Polo‐like kinase 2

Abstract

Polo-like kinases (Plks) are the key regulators of cell cycle progression, the members of which share a kinase domain and a polo-box domain (PBD) that serves as a protein-binding module. While Plk1 is a promising target for antitumor therapy, Plk2 is regarded as a tumor suppressor even though the two Plks commonly recognize the S-pS/T-P motif through their PBD. Herein, we report the crystal structure of the PBD of Plk2 at 2.7 Å. Despite the overall structural similarity with that of Plk1 reflecting their high sequence homology, the crystal structure also contains its own features including the highly ordered loop connecting two subdomains and the absence of 310 -helices in the N-terminal region unlike the PBD of Plk1. Based on the three-dimensional structure, we furthermore could model its interaction with two types of phosphopeptides, one of which was previously screened as the optimal peptide for the PBD of Plk2.

Enhancing polo-like kinase 1 selectivity of polo-box domain-binding peptides

“…The existence of “cryptic binding pockets” in the Plk2 and Plk3 PBDs have not been reported. Crystal structures of the Plk2 PBD are known, 25,26 yet these structures do not contain bound ligands and to date, no crystal structures of the Plk3 PBD have been reported. Therefore, we set out to define putative interacting residues within potential cryptic pockets of Plk2 and Plk3 and to compare them with corresponding residues in the Plk1 PBD.…”

Recent Advances and New Strategies in Targeting Plk1 for Anticancer Therapy

“…Additionally, L478, which is located at the terminus of a hydrophobic channel, appears to be important for induced-fit interactions with an alkylphenyl group on the PLHSpT-derived peptide 4j [120] (Figure 5C). In the absence of co-crystal structures of the Plk2 and Plk3 PBDs bound with their cognate ligands, specificity-determining interactions of these domains remain unknown [121, 122]. …”

Plk2 Regulated by miR-128 Induces Ischemia-Reperfusion Injury in Cardiac Cells

“…5 Plk2 has recently been discovered as a tumor suppressor associated with apoptosis. [6][7][8] Our cDNA microarray assay previously showed that Plk2 is overexpressed in transplanted heart grafts with extended cold I/R injury. 9 In this study, we aimed to investigate the role of Plk2 in cardiac cells in response to I/R injury using an in vitro cell culture model and to dissect the underlying molecular mechanism by which Plk2 induces I/R injury.…”