1. Studies of ghrelin acylation by ghrelin O-acyltransferse (GOAT).
GOAT was recently discovered1-2 as a potential drug target for curing obesity. We will investigate its molecular mechanisms and design effective inhibitors to it.
2. Mechanistic studies of polyhydroxyalkanoate (PHA) biosynthesis.
Biodegradable plastic PHAs can substitute oil-based plastics that are non-biodegradable. Our ultimate goal is to understand mechanisms of proteins involved in PHA biosynthesis and to engineer them to produce PHAs in an economically competitive fashion, which will help to protect our environment and save energy.
3. Investigation of peptidoglycan glycosyl-transferases (PGTs) in peptidoglycan biosynthesis.
PGT catalyze the final step of polymerizing Lipid II to form the nascent bacterial wall. Because their function is unique and essential for bacterial survival, PGTs have been the major target of clinically used antibiotics. Our goals are to understand the mechanism of substrate recognition by PGTs, to develop a model that can predict interactions between PGTs and substrate, and to design novel inhibitors to PGTs.
4. Site-specific protein labeling using SNAP tag.
Selective labeling of proteins has become an essential tool to visualize and characterize biological activities inside living cells. The SNAP tag was first introduced by Kai Johnsson using a human O6-alkylguanine-DNA alkyltransferase (hAGT), which transfers the alkyl group from its substrate, O6-alkylguanine-DNA to one of its cysteine residues. Our goals are to develop novel small molecule probes for specific labeling and apply this technology for detection of protein-protein interactions.
