Specific inhibition of an anticancer target, polo-like kinase 1, by allosterically dismantling its mechanism of substrate recognition. Polo-like kinase 1 (Plk1) is considered an attractive target for anticancer therapy. Over the years, studies on the noncatalytic polo-box domain (PBD) of Plk1 have raised the expectation of generating highly specific protein-protein interaction inhibitors. However, the molecular nature of the canonical PBD-dependent interaction, which requires extensive water network-mediated interactions with its phospholigands, has hampered efforts to identify small molecules suitable for Plk1 PBD drug discovery. Here, we report the identification of the first allosteric inhibitor of Plk1 PBD, called Allopole... Authors: Jung-Eun Park, Klara Kirsch, Hobin Lee, Paola Oliva, Jong Il Ahn, Harsha Ravishankar, Yan Zeng, Stephen D Fox, Samuel A Kirby, Pooja Badhwar, Thorkell Andresson, Kenneth A Jacobson, Kenneth A Jacobson, Kyung S Lee. Proc Natl Acad Sci U S A. 2023 Aug 29;120(35):e2305037120. doi: 10.1073/pnas.2305037120. Previous Science Highlights
