THE ROLE OF NONHEME IRON ENZYMES IN MULTIDRUG RESISTANCE
There is a delicate interplay of important features to consider when assessing an enzyme’s biological function, potential use in bioreactors, and biomedical applications. Structural stability is one of these. In the Meier Lab, our goal is to better understand the unfolding pathway, metal binding site, and biosynthetic mechanism of metalloenzymes that have been shown to play crucial roles in virulence enhancement and multi-drug resistance. By defining the metal-binding sites and mechanisms of these systems, we will be better equipped to identify strategies to tune function. Given that more than 30% of all characterized enzymes are metal-dependent yet less than 5% of the nearly 1500 FDA approved drugs target metalloenzymes, this work represents a critical shift in our approach to identify potential drug targets and guide the design of a generalizable mechanism based therapeutic approach.
Figure 1: Structure of CthEgtB (PDB: 6O6L) with tryptophan residues highlighted in orange. (A) Cartoon representation of CthEgtB in complex with Fe and TMH. (B) View of tetrameric CthEgtB.
