We are thankful to the National Science Foundation and National Institute of General Medical Sciences for supporting our research.
Our research continues to focus on metals in biological systems in relation to human health and the environment. Specifically, we are focused on molybdenum enzymes that plays important roles in nitrogen, arsenic and sulfur metabolism. These enzymes have a common core shown here. the cofactor contains a pterin unit and a dithiolene unit that bind metal ions. All of these components are redox active making it one of the most versatile redox active cofactors in biology. A major approach is to design and synthesis of suitable molecules probing specific components of the active sites or reactivity. In parallel, we work with the protein samples that we prepare from bacterial sources.
Periplasmic Nitrate Reductases.
Periplasmic nitrate reductase (Nap) is one of the most important bacterial nitrate reductases and are found in all phyla of bacteria. Some of the bacteria are free living while others are pathogenic. While the exact physiological roles of Nap in these bacteria are not clear, we believe that in pathogenic organisms they play an important role in nitrogen metabolism. Our research is focused on understanding the structure function roles of Nap from pathogenic organism such as Campylobacter jejuni. To this end, we have cloned and overexpressed the catalytic subunit of Nap, NapA. We investigate the properties of NapA with spectroscopic techniques.
Metal Complexes with Redox Active Ligands.
One of the redox active components in the molybdenum cofactor is the ene-1,2-dithiolene, which can exist in fully oxidized to fully reduced state. We are exploring the coordination chemistry of the fully oxidized state of the dithiolene, which is an electron deficient ligand. Coupling of this electron deficient ligand to a metal center with electron donating ligands creates donor-acceptor systems with metal center in between. These metal centers exhibit exquisite electronic properties.
Rational Synthesis of Molybdenum Cofactor.
Both nitrate reductase and arsenate reductase have molybdenum cofactor at the active site. The same basic cofactor is also present in many eukaryotic enzymes such as sulfite oxidase and xanthine oxidase. Genetic disorder leading to defect in molybdenum cofactor biosynthesis leads to several physiological disorders, yet complete chemical synthesis of the cofactor has yet not been possible. We have developing a new modular synthetic approach for this important biomolecule.
Development of new Sensors for Metal Ions.
We have developed a new class of ene-dithiols that binds metal ions very effectively. These molecules were synthesized an ongoing effort to synthesize certain features of the molybdenum cofactor. Many of the molecules are fluorophoric and we are exploring their optical properties as well as their metal binding, particularly lead binding, properties. One such molecule, called Leadglow (LG) shown here exhibit a strong preference for Pb2+ and thus acts a sensor for Pb2+.