Rongbao Li, Ph.D.

Medicinal Chemist
Protein Crystallography
Southern Research Institute
2000 Ninth Avenue South
Birmingham, AL 35205
Phone: 205-581-2555
E-mail: li@southernresearch.org

Laboratory Focus and Current Projects

The major goals of the Protein Crystallography Laboratory are to unravel the three-dimensional structures of protein molecules and to exploit the structural insight of targeted proteins for the design of therapeutic agents to treat cancer and infectious diseases. The research group focuses on protein structure analysis and structure-based design of inhibitors to target three major cellular processes: the nucleoside metabolic pathway; the folate biosynthesis/metabolic pathway; and signaling transduction pathways. In collaboration with the laboratories of Bill Parker and Joe Maddry, investigations are underway regarding the structural biology and molecular mechanisms of key enzymes in the nucleoside metabolic pathway in Mycobacterium tuberculosis.

In particular, crystals of adenosine kinase and X-ray diffraction data for determination of high- resolution structure have been obtained. The laboratory is pursuing studies of enzymes in the folate biosynthesis/metabolic pathway in M. tuberculosis, Francisella tularensis, and Bacillus anthracis. From crystals of dihydrofolate reductase from B. anthracis, the structure of dihydrofolate reductase from M. tuberculosis has been determined, leading to the discovery of novel antifolates for TB therapeutic treatment. In collaboration with scientists at The University of Alabama at Birmingham (UAB), Southern Research is pursuing the studies of structure and function of protein kinases and other signaling molecules implicated in cancer, including protein kinases C, proline-rich tyrosine kinase 2, and p130-CAS. These studies will provide molecular insights regarding the nature of protein-protein interactions or interactions between proteins and ligands and suggest a specific pharmacophore model for the drug design.

The major experimental techniques used in this laboratory include: protein over expression in both prokaryotic and eukaryotic cell systems; protein purification and crystallization; X-ray diffraction; interactive computer graphics and molecular modeling, including de novo ligand design; protein-ligand docking; and screening of three-dimensional structural databases of compound libraries.