SEMINAR: David Giedroc, PhD (Indiana Univ.)

Seminar title: “Molecular Mechanisms of Bacterial Transition Metal Homeostasis.”

First-row late d-block metals from Mn to Zn play distinct roles in cellular metabolism.  In bacterial pathogens, metalloregulation of transcription underscores physiological adaptation to host-mediated transition metal starvation and toxicity, required to maintain metal homeostasis. In zinc (Zn) homeostasis, for example, a pair of metal-sensing transcriptional repressors regulate the transcription of metal uptake and efflux transporters, where Zn allosterically activates or inhibits DNA operator-promoter binding.  I will discuss recent comprehensive NMR-based investigations of metal-mediated allostery in a number of metal-sensing transcriptional repressors. Repressor systems selected for study are representative of large bacterial repressor superfamilies, including the arsenic repressor (ArsR) and multiple antibiotic resistance repressor (MarR)-family proteins, and thus provide an opportunity to elucidate general features of metal sensing, inducer specificity and evolution of distinct biological outputs that function at the host-microbial pathogen interface.  Entropy redistribution and conformational ensemble models of biological regulation figure prominently in these repressor systems.

David P. Giedroc, Ph.D., Lilly Chemistry Alumni Professor