With this award, the Chemistry of Life Processes program is supporting the research of Professor Tom Huxford of San Diego State University to study fundamental questions in metal-mediated protein-ligand interactions. It is estimated that one third of all proteins are metalloproteins. The use of metals by antibodies to recognize and bind to antigens is a recent finding. In this context, Professor Huxford and his students have provided concrete evidence that the murine antibody LT1002 uses two bridging Ca2+ ions in binding to its antigen. Furthermore, they discovered that the amino acids involved in metal coordination by LT1002 are encoded in the germ-line sequences of antibody genes within the genomes of diverse mammalian species and are also present in several antibodies that have been previously analyzed. The experiments to be performed under this award are designed to characterize the metal binding potential of the LT1002 antibody and to test the hypothesis that the use of metals by antibodies to recognize their antigens is evolutionarily conserved within the mammalian immune system.
The Broader Impacts of this proposal center upon the design of experiments that can be carried out by undergraduate and Master's degree candidates in collaboration with local industrial scientists. The overall educational goal of Dr. Huxford's research program is to expose a broad number of diverse students to principles of structural biochemistry at an early stage in their academic careers. The Structural Biochemistry Laboratory, in which the proposed research will be carried out, has established and continues to maintain the SDSU Macromolecular X-ray Crystallography Facility that serves biological and chemical researchers across campus. Dr. Huxford has organized the SDSU Structural Biology Program, an informal association of SDSU molecular biology students, faculty, and researchers who meet together and host lectures and seminars aimed at improving their understanding of experimental approaches that link biomolecular structure and function.