Current Research Interests

Introduction- In general, a very broad description of the work of interest to this laboratory are the mechanisms of metalloproteins involved in radical generation, oxidative stress protection, as well as heme synthesis, sensing, aquisition and transport.

With very few exceptions, heme is required by most organisms for a vast array of heme dependent enzymes and biosensors. More recently, a number of heme regulated pathways have been identified that have a far reaching impact on human health. Areas of focus range from heme aquisition and sensing by both bacterial (pathogenic) and human systems to the heme regulated activities of cytochrome P450s involved in cholesterol biosynthesis and the degradation of chemotherapeutic compounds in humans.

We are also interested in the atomic details of radical generation and transfer in the family of glycyl radical containing enzymes. These enzymes are activated by an activating enzyme that utilizes a [4Fe-4S] cluster to catalyze the reductive cleavage of S-adenosylmethionine (SAM). Similar to heme function, these enzymes are widespread in Nature and serve to catalyze a number of difficult and essential reactions. Of particular interest is the mechanism by which a radical SAM enzyme "activates" another enzyme through protein-protein interactions and transfer of a highly reactive radical.

 

Research Techniques- A central technique employed by this laboratory is X-ray crystallography and single crystal methods. However, in keeping with a prevalent theme at the University of Georgia, many of these systems involve metalloenzymes and are therefore amenable to many spectroscopic methods. The information that is gained through the crystallographic models is then complemented by techniques in biophysical spectroscopy. A strong resource in this area is the Center for Metalloenzyme Research here at UGA.

 

Research Projects- The following research areas are currently being investigated.

1) The Terminal Steps of Heme Biosynthesis and Heme Biosensing

2) The Role of Fe-S Clusters in Radical Chemistry: The
1,3-Propanediol Pathway in Clostridium butyricum