University of North Carolina at Chapel Hill
Talk Session: SESSION 12: PEPTIDE DESIGN AND FUNCTION
Date: Wednesday, June 15, 2022
Talk Time: 03:25 pm - 03:50 pm
Talk Title: Determining What Else Trimethyllysine Reader Proteins Can Read
Our group is an interdisciplinary group, focusing on problems of molecular and biomolecular recognition. Molecular recognition impacts a wide range of fields, including asymmetric catalysis, materials chemistry, and protein folding. Consider, for example, designing a drug to bind to the active site of an enzyme. What features other than shape might contribute to binding? What types of interactions will provide high affinity as well as high selectivity? These are general questions in the field of molecular recognition that we are investigating for applications to biosensing, drug delivery, and de novo protein design.
The research interests in our group span a wide range, from mechanistic organic chemistry and molecular recognition to structural biology, and hence involve the use of a variety of techniques. Methods used in our group include organic and solid phase synthesis, combinatorial chemistry, computational chemistry, molecular biology, kinetic and thermodynamic measurements using 1D and 2D NMR, circular dichroism, UV/Vis and fluorescence spectroscopy, analytical ultracentrifugation, and calorimetry. The extent that any one student uses these techniques depends largely on the particular student's research interests.
Post-translational modification of histone proteins, including lysine methylation, regulate gene expression through recruitment of reader proteins to the nucleosome. Dysregulation of these events is prevalent in a wide range of diseases, such that there is much interest in developing selective inhibitors and probes for this class of proteins. However, with over 200 methyllysine reader proteins in humans, achieving selectivity can be challenging.
We have taken a mechanistic approach coupled with high throughput screening to identify unique selectivity patterns in these proteins, establishing new mechanisms of action and providing new opportunities for selective inhibition. These findings will be discussed.