Prof David Giedroc

MoSE 3201A
Tuesday, December 3, 2019 - 4:00pm to 5:00pm

Allostery and bioinorganic switches: New insights into 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 drives physiological adaptation to host-mediated transition metal starvation and toxicity, required to maintain metal homeostasis.  We are currently working on two separate aspects of this problem.  In the first, we are employing global multi- ‘omics strategies to elucidate metabolic adaptation to host-mediated transition metal starvation.  In the second, we are employing advanced NMR approaches to understand transition metal sensing at the physicochemical level.  In bacterial 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 present the results of 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.   

Contact Information: 
Host:  MG Finn (
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