Figure 1.

A schematic diagram illustrating the domain structures of the human polo-like kinase (PLK) family of proteins (PLK1-5). The number of amino acids in each family member is indicated on the right. The location of the kinase domains is shown in orange, whereas the polo-box domains (PBD), made of two polo-boxes (PB), are represented in blue. These two domains are separated by the interdomain linker, which comprises a destruction box (D-Box) indicated in green. The numbers indicate the first and the last residues of these domains in human PLKs. Residues that are essential for ATP-binding and enzymatic activation (T-loop) within the kinase domains, and for phosphoselectivity within the polo-box domains, are depicted. Sequence identities with the corresponding domains in PLK1 are provided in percentages. Two distinct strategies for targeting PLK1 are included: ATP-competitive inhibitors targeting the catalytic activity of PLK1, and PBD-binding antagonists competitively inhibiting the function of PBD.