The overall aim of this project is to characterize the galectins, a family of animal proteins with calcium-independent affinity for lactose and other beta-galactosides (previously called S-Lac lectins or SD-type lectins). These are unusual abundant cytosolic proteins with possible intracellular functions, but which are also secreted (by a non-classical pathway) and interact with extracellular glycoconjugates to modulate cell adhesion in epithelial cells and other cells. Several galectins have been cloned and expressed in iE.coli.The recombinant proteins are used for structural studies by X-ray crystallography and NMR in collaboration with Drs. Jim Rini and Jeremy Carver at the University of Toronto. One galectin X-ray crystal structure has been published by us and another by others. Recently, our collaborators have solved the structure of three additional different galectin carbohydrate binding domains including complexes with oligosaccharides. The Computer Graphics Laboratory resources are used to display the structures of these lectins, and to do further modeling of their interactions with their ligands, in part aiming at design and synthesis of better inhibitory ligands for galectins. This includes molecular modeling in collaboration with the group of Professor Kuntz, UCSF.
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