Victor L. Hsu
Victor L. Hsu
Ph.D. 1989, University of California, San Diego
Our laboratory is interested in studying the structural aspects of biomolecular recognition and interactions, especially in protein-nucleic acid complexes. These interactions account for many of the major cell functions such as the induction or repression of gene expression and the packaging of nucleic acids into other superstructures. The primary technique that we use is nuclear magnetic resonance (NMR) spectroscopy, which is uniquely suited for studying biomolecular structures at atomic resolution. We are studying both sequence-specific and nonspecific DNA-binding proteins and have been active in developing isotope-edited NMR strategies to obtain more accurate distance constraints for use in structure calculations, and to investigate the intrinsic flexibility of protein and DNA backbones. We utilize wild-type and mutant DNA-binding proteins to provide insights into which factors most affect protein stability and how DNA-binding is mediated. Another approach that we employ to better understand the molecular recognition of DNA is to determine the detailed structures of DNA-drug complexes. Certain antitumor agents bind to specific sequences of DNA, and we are investigating how modifications of these sites affects recognition, binding and activity. Finally, conformational changes associated with changes in the local solvent environment and the ability for certain protein sequences to fold into different structural elements is being studied using model peptides and intact proteins. The relationship between this phenomenon and protein interactions is being investigated.