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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.

Also ubiquitous in nature are metals, so a fundamental question arises regarding their roles in sulfation. Kinetics work, microcalorimetry, and fluorescence titrations have revealed the non-competitive mechanism whereby zinc (2+) potently inhibits SULT1A1.

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.

Finally, we are looking for proteins that interact with SULT1A1. Two-hybrid screening is about to begin.

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

Alma has had lasting relationships with colleges and universities in South Korea, with the Korean international students completing one full year of study at Alma. Here at Alma, the international students make lifelong friendships and leave everlasting impacts on our students and on the surrounding communities.