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My primary teaching duties of Biochemistry, Molecular Genetics, and Toxicology are laced with an active research program. What happens to the Tylenol that you swallow? It is primarily metabolized by the covalent attachment of sulfate, and we study the enzyme that catalyzes this reaction. Sulfotransferases (SULTs) are actually found throughout biology, and this genetically-related family of enzymes plays many important roles. But our focus is primarily on a prototypical member that prefers simple phenols, SULT1A1.

The students in my lab continue to discover properties of SULT1A1 that likely contribute to its activity, mechanism, and regulation. For example, the ubiquitous coenzyme A (CoA) is an inhibitor, and its potency is augmented when esterified with long chain fatty acids. Furthermore, CoA can form a covalent adduct with the enzyme under non-reducing conditions. Molecular modeling and site-directed mutagenesis studies provided an explanation for these observations.

Consideration of SULT structures reveals some interesting exon-based functional domains. Students have recently constructed SULT1A1 mutant libraries of a loop that we hypothesize functions as a mobile lid over the enzyme active site. Possible effects of these changes will test this idea.

Nature's accomplishments have reasons, so what is the advantage in having SULTs appear as dimers? Using gene engineering, we have converted SULT1A1 into two classes of monomeric enzymes that spontaneously dimerize when mixed. Comparing the activities, rapid kinetic, and thermodynamic behaviors of these enzymes will clarify the role of quaternary structure in SULT catalysis.

We are also questioning the currently-accepted base-catalyzed mechanism proposed for SULTs. Site-directed mutagenesis, followed by kinetics studies, have suggested an alternative possibility. A novel rapid kinetics method will be used to test it.

In addition to SULT-centered projects, we collaborate with other faculty and their projects. For example, an ongoing effort exists with Dr. Turk (Chemistry) as we explore potentially new inhibitors of the influenza virus N1 neuraminidase enzyme. Also, engineering cancer gene knockout (gene disruption) vectors is in progress with Dr. Calhoun (Biology).

Enzyme mechanisms, Xenobiotic metabolism, Steady State and Rapid kinetics, Molecular genetics, Gene isolation methods, Mutagenesis, Gene regulation

As an undergraduate student studying mathematics at Wuhan University in China, Zhewei Dai was so inspired by her own professors that she determined she would follow in their footsteps.

“I wanted a career in which I would have lifelong learning and an intellectual challenge,” she says. “I wasn’t interested in the 9-5, then repeat, same everyday lifestyle. I also had wonderful teachers who shaped me, and through them, I realized teaching was an important and honorable profession.”