Professor Troy Stich
Department of Chemistry
Wake Forest University
George P. Williams, Jr. Lecture Hall, (Olin 101)
Wednesday, Oct. 9, 2019, at 3:00 PM
There will be a reception in the Olin Lounge at approximately 4 PM following the colloquium. All interested persons are cordially invited to attend.
ABSTRACT
The radical SAM (S-adenosyl-L-methionine) superfamily of enzymes catalyzes a dizzying array of chemistries triggered by reductive cleavage of SAM to yield the primary carbon radical 5′-deoxyadenosyl (5’dAdo●). 5’dAdo● can pluck off H-atoms with bond dissociation enthalpies <105 kcal/mol from substrate molecules to initiate carbon skeleton rearrangements. We hypothesize that amino acids within the active site, a triose phosphate isomerase (TIM) barrel, are key in conducting these rearrangements down the evolutionary-designed path. Our research effort employs a combined biochemical, spectroscopic, and computational approach to determine atomic level details of these mechanisms. We further use substrate analogs that can slow or halt the chemistry at key points, allowing us to verify mechanistic hypotheses. Today, I will present a few examples that illustrate our progress toward unveiling the factors that control these exotic reactions.