IMPRS Distinguished Guests Seminar Series

Protein phosphatases dephosphorylate proteins and, as counter players of kinases, play key roles in essential cellular processes. Their dysregulation contributes to diseases such as cancer, immune diseases, and heart failure. Accordingly, there is a great interest to study their mechanisms and druggability, as well as to validate them as disease targets.1 While kinases share the catalytic mechanism, phosphatases have evolved from different ancestors and function through different catalytic mechanisms, which they share among their smaller families. We classified these and listed them in our open access database www.DEPOD.org, which also includes their substrates and other information.2 Two major families are the phospho-serine/threonine-specific phosphoprotein phosphatases and the largely phospho-tyrosine-specific protein tyrosine phosphatases. Our work focuses on specific phosphatases of these families. We develop peptides, peptidomimetics and small molecules as research tools to enable targeting these challenging enzymes.3,4 Using these tools, we study phosphatases on the molecular and cellular level, and we also devise phosphoproteomic strategies to provide insights into their substrates and affected pathways.5,6 I will discuss our interdisciplinary work exemplified through the ubiquitous phosphatase PP1.

_{[1] M. Köhn, ACS Cent. Sci. 2020, 6, 467-477.
[2] N. Damle, M. Köhn, Database (Oxford). 2019, 2019, baz133.
[3] J. Chatterjee, M. Beullens, R. Sukackaite, J. Qian, B. Lesage, D. Hart, M. Bollen, M. Köhn, Angew. Chem. Int. Ed. 2012, 51, 10054–10059.
[4] B. Hoeger, M. Diether, P.J. Ballester, M. Köhn M. Eur. J. Med. Chem. 2014, 88, 89-100.
[5] B. Hoermann, T. Kokot, D. Helm, S. Heinzlmeir, J.E. Chojnacki, T. Schubert, C. Ludwig, A. Berteotti, N. Kurzawa, B. Kuster, M.M. Savitski, M. Köhn, Nat. Commun. 2020, 11, 3583.
[6] B. Hoermann, E.-M. Dürr, C. Ludwig, M. Ercan, M. Köhn, Chem. Sci. 2024, 15, 2792-2804.}