Biophysical Studies on the Interactions of Bacterial Toxins

Many diarrhoeal diseases such as cholera are caused by protein toxins that have an AB5 hetero-oligomeric structure. The proteins comprise a single toxic A-subunit and a pentameric B-subunit that interacts with specific cell surface glycolipids. Inhibitors of such protein-carbohydrate interactions could provide prophylactic treatments for these debilitating diseases. In our work we aim to understand the binding interactions of multivalent inhibitors for bacterial toxins. Often a single biophysical technique is limited in the information it can provide, whereas a more complete picture can be constructed through an integrated approach using a broad range of biophysical methods. For example, the importance of protein and ligand dynamics in multivalent interactions is revealed when combinations of NMR spectroscopy, isothermal titration calorimetry, analytical ultracentrifugation and dynamic light scattering are used to study to different multivalent systems.