|Ph.D||Texas Tech University||2002|
|M.S.||Hanyang University, Seoul||1996|
|B.S.||Hanyang University, Seoul||1994|
|Postdoctoral Fellow?research Associate||Texas Tech University||2002-2007|
|Assistant Professor of Biochemistry||Baylor University||2007-|
APS reductase is a key enzyme in the sulfate assimilation pathways in bacteria, algae, fungi and plants. We are attempting to elucidate the mechanism of APS reductases using bacteria expression system. We are studying the electron transfer in APS reductases, looking at the dithiol/disulfide couple and [4Fe-4S] cluster in the mechanism. In addition, X-ray crystallography and NMR spectroscopy have been used to understand the structure of enzymes.
In particular, the APS reductase from Pseudomonas aeruginosa, a pathogenic bacterium causing urinary tract infections, respiratory system infections, dermatitis, soft tissue infections, bacteremia, bone and joint infections and gastrointestinal infections in humans. APS reductases catalyze the reduction of APS to AMP and sulfite, using reduced thioredoxin as an electron donor. As humans do not have APS reductase, finding a potent and specific inhibitor of Pseudomonas aeruginosa APS reductase may allow development of a drug that is lethal to the bacterium without producing harmful side-effects on human patients infected by P. aeruginosa. We propose to find possible drugs using SELEX (Systematic Evolution of Ligands by Exponential enrichment), an in vitro selection technique that allows screening for a particular functionality, such as the binding to proteins. Functional molecules, called aptamers, that are suitable for the enrichment of any desired property are selected from a large, random pool of RNA or DNA (the great majority of pool members are non-functional) by column chromatography or other selection techniques. The immense complexity of the generated pool justifies the assumption that is may contain a few molecules with secondary and/or tertiary structures that will allow tight and highly specific binding to a target enzyme, resulting in inhibition of the enzymatic activity.
Another project that we have investigated is proteomics studies of glutaredoxins and glutaredoxin-dependent proteins. The genome of the cyanobacterium Synechocystis sp. PCC 6803, an oxygenic phototroph, endodes three glutaredoxin (Grx) proteins, some of which are likely to be implicated in redox regulated signaling pathways that respond to reactive oxygen species (ROS). We propose to develop global methods for identifying the complete set of Grx-interacting proteins in Synechocystis sp. PCC 6803. The use of a mutated Grx affinity column, combined with the use of mass spectrometry to identify the proteins bound by the column, should prove to be a highly effective method for identifying the Grx-interaction proteins. The set of Grx-interacting proteins for all three Grx genes in Synechocystis sp. PCC 6803 will provide insight into how Grxs recognize and target proteins for reduction. In addition, this study will identify new redox-regulated proteins, which will be further characterized structurally and functionally. Development of approaches to identify relevant Grx-targets in Synechocystis sp. PCC 6803 can then be applied to other higher eukaryotes to identify novel redox proteins and signaling pathways.