Structure-Guided Inhibitor Design on RNA Modifying Proteins
We determine structures of protein-inhibitor complexes using X-ray crystallography to guide development of anti-cancer and anti-viral compounds. We focus primarily on DNA or RNA binding proteins, which play important roles in gene regulation and disease development.
Shifali Shishodia, Marina Demetriades, Dong Zhang, Nok Yin Tam, Pratheesh Maheswaran, Caitlin Clunie-O’Connor, Anthony Tumber, Ivanhoe K. H. Leung, Yi Min Ng, Thomas M. Leissing, Afaf H. El-Sagheer, Eidarus Salah, Tom Brown, Wei Shen Aik*, Michael A. McDonough*, and Christopher J. Schofield*. Structure-Based Design of Selective Fat Mass and Obesity Associated Protein (FTO) Inhibitors. Journal of Medicinal Chemistry 2021 64 (22), 16609-16625. https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.1c01204
Structural Biology of Protein-RNA Complexes
We are intrigued by how proteins regulate genes on the RNA transcript level, especially through post-transcriptional modifications. In this area of research, we investigate how molecular machines that modify RNA using structural biology techniques such as protein crystallography and cryo-electron microscopy. We are also interested in investigating how viruses modify RNA.
Simranjeet Kaur, Nok Yin Tam, Michael A McDonough*, Christopher J Schofield*, Wei Shen Aik*, Mechanisms of substrate recognition and N6-methyladenosine demethylation revealed by crystal structures of ALKBH5–RNA complexes, Nucleic Acids Research, 2022;, gkac195, https://doi.org/10.1093/nar/gkac195
Macromolecular Assembly Engineering
We are also exploring the use of macromolecules as drug delivery agents. We take advantage of structural biology and biophysical techniques to guide our design.