Zucai Suo

Research Description:

The research in my laboratory has three major directions: to elucidate kinetic mechanisms of enzymes involved in DNA/RNA replication, repair, and lesion bypass; to understand Hepatitis C (HCV) replication and regulation of innate immunity; to develop antiviral and anti-cancer molecules based on rational drug design.

The Suo lab utilizes a variety of multi-disciplinary techniques to investigate intriguing questions in enzymology and to pursue rational drug desing. Pre-steady state kinetic methods are employed using rapid chemical quench-flow and stopped-flow. These methods allow us to quench reactions on the millisecond time scale and to extract more kinetic information than the traditional steady-state kinetic methods. We also use protein engineering methods including site-directed mutagenesis and domain-swapping to study structure-function relationships of DNA polymerases. Single molecule FRET spectroscopy is used to investigate the kinetics and dynamics of individual protein molecules to reveal molecular details undetectable in bulk ensemble experiments. X-ray crystallography is being used to examine interesting enzyme-substrate complexes. These multi-disciplinary approaches will allow us to develop new methods and to advance enzymology into unprecedented territory. Our goals are to understand the elementary steps of conformational changes and chemical reactions occurring at the active site of enzymes. Our understanding of the kinetics, structure and dynamics of these enzymes is ued for rational drug design. The designed enzyme inhibitors are being synthesized and tested in vitro and in vivo.