Congratulations to Amy Overstreet and Laura Ingersol for winning the Smith/Dow award for 2020!
Posted: Nov 16, 2020 - 12:00am
Amy Overstreet has made overwhelming progress in the CCB program. She has completed two first author manuscripts, one has been accepted and the other is currently under review. Amy has been developing computational chemistry tools to study PDZ protein domains. PDZ domains are highly abundant protein-protein interaction domains found in signaling proteins and play a critical role in many biological processes such as managing cell polarity, regulating tissue growth and development, trafficking of membrane protein receptors and ion-channels, and regulating cellular pathways. Despite the importance of the PDZ protein family, few computational efforts have been put towards the understanding the molecular functions PDZ domain. Amy’s work focuses on the changes in structure and dynamics of PDZ domain upon ligand binding, and she has provided a thorough analysis of both dynamic changes and electrostatic allosterism of the PDZ domain. This work is significant and contributes a more complete understanding of allosterism across this important protein family and could lead to new therapeutics to combat drug and substance addiction.
Laura Ingersol has been working on two extremely difficult bioinorganic projects, and she has made considerable progress on both. Her projects have focused on pyranopterin containing molybdenum (Mo) enzymes, which are widely found in bacteria, archaea, and eukarya. Humans possess four of these enzymes, which function to hydroxylate a wide variety of purine-based drugs and heterocyclic metabolites, oxidize aldehydes, detoxify sulfite by oxidizing it to sulfate, and synthesize the biological messenger molecule nitric oxide via the one-electron reduction of nitrite. The importance of Moco in humans is exemplified by the fact that mutations in the Moco biosynthetic pathway lead to Moco deficiency, a severe neonatal metabolic disorder that results in neurodegeneration and infant death due to a loss in sulfite oxidase (SO) activity. Laura is the first author on two manuscripts that have provided new insights into the chemical functions of the molybdenum enzymes.