Though transition metal ions play an essential role in many cellular processes, they are extremely toxic at high concentrations. Biological metal ion homeostasis maintains the intracellular concentrations of these metal ions through a number of metal sensor proteins that regulate the expression of genes that encode specific transition metal efflux and sequestration proteins. Using computational tools, we will describe and discuss how prototypical transition metal ion transcriptional repressors of the ArsR family of transcriptional repressor proteins carry out their function. In particular, the role of allostery and the function of a key hydrogen bond connecting the metal binding domain with the DNA recognition domain will be discussed. The second half of the talk will focus on the novel Cu(I) transporting protein CusF, which has at its metal binding site a biologically novel p-complex between the metal ion and an indole side chain from Trp44. The mechanism by which CusF delivers the Cu(I) ion to its biological target, the CusABC transporter, will be discussed. Finally, we will describe a novel antibiotic strategy that involves the alteration of the transition metal ion balance in a cell via the disruption allosteric changes involved in the transition metal homeostatic machinery.<br/>

Allostery driven by metal ions: Getting transition metal ions around cells safely

253rd National Meeting (2017)

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