The broad research interest of my group centers around protein ubiquitination and its relationship with bacterial pathogens. Specifically, understanding mechanism of action of deubiquitinases (DUBs) and ubiquitin modifying enzymes of both prokaryotic and eukaryotic origin. Using crystallography, biochemical and biophysical data we wish to unravel mechanism of action of these enzymes, including regulation of catalytic activity and substrate selection. The fact that viruses and bacteria manipulate our ubiquitination pathways has been known for at least two decades, with a number of well characterized examples of pathogens using enzymes or substrate adaptors to co-opt our ubiquitination pathways.

Despite the diverse nature of these pathogenic factors, they seem to have converged on a broadly similar formula of operating within the context of their eukaryotic host’s ubiquitination mechanism. However, over the past five years there has been a remarkable shift in our understanding of ubiquitination, thanks to the discovery of novel mechanisms of ubiquitination catalyzed by bacterial effectors.

Elucidating the mechanism of ubiquitination by MavC (Puvar & Iyet et al., 2020)

We are engaged in dissecting the mechanism of these enzymes, specifically, how their catalytic activities are regulated. The enzymes we are studying are known to be activated when they associate with larger macromolecular complexes. We use X-ray crystallography in conjunction with a variety of structural, biochemical, and biophysical techniques to accomplish these goals.

Our lab has to this date crystallized more than 50 crystal structures of proteins that regulates the ubiquitination pathway. As part of the Chemistry Department at Purdue University, we have access to numerous facilities on campus. In addition, our location is conveniently only two hours away from the Argonne National Lab.