9:50 AM - 10:40 AM Session Chair: Chung Hwan Cho, Ph.D.

Chemical Tools for Protein Histidine and Arginine Phosphorylation

Jung-Min Kee, Ph.D. 기정민 (奇定民) Associate Professor

Department of Chemistry Ulsan National Institute of Science and Technology (UNIST) Website: http://kee-lab.org E-mail: [email protected]

Abstract

Despite the well-recognized biological importance of protein phosphorylation, non-conventional forms of phosphorylation on histidine residues has evaded our attention and scrutiny for a long time. This gap in our understanding stems from the inherent chemical instability of phosphohistidine (pHis), making the investigation of these forms of phosphorylation notoriously challenging.$^1$

We present novel chemical tools to tackle this historically elusive protein modification here. First, we describe convenient activity assays to monitor the phosphorylation and dephosphorylation of His in real-time. Our assays were successfully employed for the biochemical characterization and inhibitor discovery of the corresponding kinases and phosphatase. We will also describe the extension of our work to protein phosphorylation.

References

1 Kee, J.-M.; Muir, T. W. ACS Chem.Biol., 2012, 7, 44–51.

2 Ahn, S.; Jung, H.; Kee, J.-M. ChemBioChem, 2021, 22, 319–325.

3 Choi, Y.; Shin, S. H.; Jung, H.; Kwon, O.; Seo, J. K.; Kee, J.-M. ACS Sens., 2019, 4, 1055–1062.

4 Lee, D.; Lee, Y.; Shin, S. H.; Choi, S.; Lee, S. H.; Jeong, S.; Jang, S.; Kee, J.-M. Bioorg. Chem. 2023, 130, 106232.

5 Kim, H. J.; Jung, H.; Kim, S.; Seo, J. K.; Kee, J.-M.* ACS Med. Chem. Lett. 2022, 13, 1911–1915.

6 Choi, S.; Ahn, S.; Cho, K. H.; Lee, S. K.; Kee, J.-M. ChemRxiv 2024 (10.26434/chemrxiv-2024-vh5mm-v3)