Biochemists and structural biologists have learned a tremendous amount about a common group of calcium-binding proteins containing the """"""""EF-han motif"""""""" (troponin C, parvalbumin, calmodulin, etc.) from which there is a relative wealth on information on their structures and function. However another unique group of proteins exist, the calcium-binding a-lactalbumins and lysozymes, which are """"""""non-classical"""""""" calcium-binding proteins which have a unique and distinct coordination geometry. The overall topography and role of the cation binding loop in the calcium-binding alpha-lactalbumins has yet to b fully understood. Furthermore, the alpha-lactalbumins are unique in their high propensity to form the intermediate """"""""molten globule"""""""" folding state. They also bind the metal ion zinc at another distinct site, which modulates the conformational properties of the calcium bound form.
The aims of this project are to unravel the structural and functional properties of the calcium binding properties of this milk protein, which modifies the specificity of the enzyme galactosyl transferase in lactose biosynthesis.
The specific aims of this project are to: 1. Unravel the determinants involved in calcium binding (and in the folding an structural integrity of the protein). 2. Determine which residues of the protein are buried in membranes. 3. Determine the role of the amino acids involved in zinc binding.
