2025/11/10 by Uwe Eberspaecher, Arndt A. Schmitz, Gerhard Siemeister +5 · 1 voice
Biochemistry, Genetics and Molecular Biology · Environmental Science · #Microtubule and mitosis dynamics #Bacteriophages and microbial interactions #Advanced Electron Microscopy Techniques and Applications
paper · doi:10.1107/s2059798325009325
openalex publication_date 2025/11/10 · openalex created_date 2025/11/18 · openalex updated_date 2026/07/23
Polo-like kinase 1 (PLK1) is a major regulator of cell division and has been pursued as a drug target for cancer therapy for a long time. Crystallization of the kinase domain has proven to be exceptionally challenging. Previously, we published a crystallization approach using a PLK1-specific designed ankyrin-repeat protein (DARPin) as a crystallization facilitator. Here, we report an alternative route: crystallization was successful after the introduction of a double mutation which reduced surface entropy and enabled the formation of a new crystal contact. This new PLK1 crystallization system was used to determine the first co-complex crystal structure of the Bayer thiazolidinone lead series, as well as crystal structures with representatives of two competitor inhibitor series. The molecular binding modes of these three inhibitors are analysed and discussed, and the surface-entropy reduction approach is compared with the surface modifications employed by us and others to enable the crystallization of PLK1.