TIME CHANGE | What Part of •NO Don’t You Understand?

OPEN TO PUBLIC | Susan M. Mitroka, Ph. D., an associate professor from Worchester State University, will be joining us to discuss What Part of •NO Don’t You Understand?: The Chemistry of Nitric Oxide Derivatives and Their Pharmacological Properties. Snacks will be provided. 

Nitroxyl (HNO), the simplest nitroso compound, reacts as a potent electrophile and rapidly forms addition products with nucleophiles. In biomolecules, these reactions are particularly observed with thiols from the amino acid cysteine, leading to enzymatic inactivation of many proteins. While the reactions of thiols and HNO have received much attention, little is known about the reactions of selenium-based compounds and HNO. The basic chemical properties (increased acidity and polarizability leading to enhanced nucleophilicity) indicate that selenium-containing proteins would be a preferred target of HNO suggesting the possible selective inhibition of seleno-enzymes with HNO based compounds. Of specific interest to my research group is the enzyme Thioredoxin Reductase 1. Thioredoxin Reductase (TrxR), a seleno-enzyme with a selenocysteine active site necessary for enzymatic activity, contributes to antioxidant defense and cell growth and has been linked to both the prevention and progression of cancer. The unique chemical composition of TrxR1 and its link to cancer progression make inhibition of this redox protein an attractive anti-cancer strategy. The increased amount of this enzyme found in cancerous cells, in addition to its anti-apoptotic involvement in the cell cycle, contributes to its desirability as a target for therapeutic agents, thus inducing apoptosis in a cancerous cell line or reducing the resistance to other chemotherapeutic drugs. Given the unique chemical nature of the enzyme active site, irreversible modification through an electrophilic agent promises to be a viable means of deactivating the protein. Our preliminary work indicates in vitrodeactivation of this protein via HNO. Current chemical and computational studies are further developing the reaction rate, transition state energy and overall affinity of this selenoprotein for nitroxyl.

Please note: There will be a shuttle offered to students attending this event who also wish to attend the Climate Strike event immediately following. The shuttle will be picking up at the Flagpole.