Bioinorganic Chemistry Seminar: Professor Maria-Eirini Pandelia, Brandeis University

About the Seminar

Is metal a choice?

The first part of the talk is focused on the Fe and Zn cofactor dilemma. Fe and Zn are essential enzymatic cofactors across all domains of life. Although they share commonalities, their chemical roles in the nascent protein scaffolds are generally considered mutually exclusive. Fe and Zn ions in metalloproteins are found to be utilized both selectively and interchangeably, invoking the notion that Fe and Zn may functionally substitute for each other depending on the cellular conditions and may represent different states in enzyme evolution. The second part of the talk explores ideas about how Iron and Manganese, metal ions essential to life, are intimately linked to inhibition or aberrant activation of clinically important cellular pathways. In addition, it explores the evolutionary sophistication in metal- and nucleotide-dependent allostery. The system of study is the superfamily of SAMHD1 dNTPases for which the role of metal ions in infectious disease and innate immunity remain largely undefined, while the potential of these enzymes as targets for the development of antiparasitic and therapeutic drugs is largely unexplored.

About the Speaker 

My work is centered on delineating the mechanisms according to which metalloproteins involved in processes essential for life perform the activation of small (or larger) molecules, how the specific identity of the metals in the active sites allows their chemical diversion and selectivity and what the functional role of iron-sulfur clusters in proteins involved in DNA synthesis and repair is. The research of the group revolves around proteins that are candidates to be the targets of new antiviral factors and to mediate DNA modifications and other important chemical transformations. These proteins often belong to large structural superfamilies with apparently similar representatives that are carrying out radically different reactions. We want to understand those functions and the extant determinants that endow this chemical versatility.

Host: Laura Dassama