Brief Description of our ResearchWe use structural biology techniques to elucidate the mechanism and function of biological macromolecules.
A major focus of our current research is on enzymes that are involved in fatty acid and/or carbohydrate metabolism. These include acetyl-coenzyme A carboxylase (ACC), carnitine acyltransferase, AMP-activated protein kinase (AMPK) and others. These enzymes are important targets for drug discovery against obesity, diabetes and other human diseases. The goals of our research are to produce structural information on these enzymes and to understand their functions at the molecular level. The structural information will also lay the foundation for drug discovery against these targets.
Another area of our research is on proteins involved in pre-mRNA 3'-end processing. Most eukaryotic mRNA precursors must undergo cleavage and polyadenylation in their 3'-ends before they can function as mRNAs. This processing machinery contains more than 16 protein factors, which form several sub-complexes (CPSF, CstF). The goal of our research is to understand the molecular basis of this important event. We will produce crystal structures of the protein subunits, protein-protein complexes, and protein-RNA complexes, and carry out functional studies to assess the structural information.
Our recent studies unexpectedly led to the identification of an mRNA 5'-end capping quality control mechanism. We have identified the enzymes (Rai1, Dxo1, DXO) that play a central role in this mechanism. We are characterizing their biochemical properties and deciphering their physiological functions in yeast as well as mammalian cells.
The cyclic dinucleotide c-di-AMP is an allosteric regulator of metabolic enzyme function.
Cell, 158, 1389-1401 (2014).
T.H. Tran, Y.-S. Hsiao, J. Jo, C.-Y. Chou, L. Dietrich, T. Walz & L. Tong.
Structure and function of a single-chain, multi-domain long-chain acyl-CoA carboxylase.
Nature, 518, 120-124 (2015).