Event Information
Thermodynamic Additivity: Part 1: Galectin 3; Part 2: Intramolecular Systems (SH2 Domain)
- Abstract:
Non-covalent association events in aqueous solution control most biological interactions. However, the thermodynamic basis of selectivity and affinity in these events is poorly understood. This work investigates the molecular basis of these events through analysis of the origins of additivity through multivalency. Protein-carbohydrate interactions, although generally weak-affinity, can affect biological systems through significant increases in affinities upon binding tethered multivalent ligands. Unique carbohydrate binding protein Galectin-3 is a model of conditional multivalency, in that the aggregation and ligand binding properties of the protein can be modulated independently. We have provided evidence that protein-protein interactions leading to aggregation are responsible for the observed enhanced affinities through isothermal titration calorimetry with a series of monovalent and multivalent ligands.
In a second project, the thermodynamic consequences of linking two or more conceptual fragments of a ligand in the binding site of a protein are examined. This was surprisingly demonstrated to be an enthalpically driven phenomenon. Current work investigates the origins and consequences of additivity in ligand binding using the Src SH2 domain through isothermal titration calorimetry and X-ray crystallography.
Preliminary Examination Seminar
Student Exams Seminar