Structural Biology and X-Ray Crystallography

The human body is comprised of billions of tiny molecular structures, or proteins, each with a unique three-dimensional shape suited to its specific function in the body. The effect on human health can be significant if the shape of even one protein goes awry. Misshapen proteins, especially those comprising the cell surface or cell membranes, are believed to play a causative role in many diseases, including cancer and Alzheimer's disease. Structural biology is devoted to mapping and studying the molecular structure of biological proteins to determine how a change in structure affects the function of these proteins in the body. This information is used to design therapeutic agents that will target certain proteins for the treatment of disease. X-ray crystallography is a powerful and highly precise imaging technique used in structural biology to identify the three-dimensional structure of a molecule or macromolecule (protein). The first tool used to discover the structure of DNA, this advanced technique involves subjecting the sample to an intense beam of x-rays of a uniform wavelength in order to produce a diffraction pattern that is analyzed to determine a precise molecular structure.

Focused Research and Advanced Capabilities

The primary goals of the Southern Research structural biology and x-ray crystallography laboratory are to unravel the three-dimensional structure of protein molecules and to exploit the structural insight of the targeted proteins; this information is used to design therapeutic agents to treat cancer and infectious disease. Utilizing a state-of-the-art laboratory, our highly skilled scientists focus 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. Using X-ray crystallography, we have determined the crystal structures of human proline-rich tyrosine kinase in addition to adenosine kinase and ribokinase from Mycobacterium tuberculosis. These studies provide molecular insight regarding the nature of protein-protein interactions or interactions between proteins and ligands in addition to suggesting specific pharmacophore models for drug design.

We offer clients diverse experimental techniques including:

• Protein overexpression 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
• Screening of three-dimensional structural databases of compound libraries