Proteins are biological polymers with essential functions in the maintenance of life on earth. Their catalytic and structural roles in biological organisms are tightly coupled to the primary sequence of their constituent amino acid building blocks, which determines the three-dimensional fold of the protein. However, the conservative nature of the genetic code limits the available amino acids from which proteins may be constructed to only twenty different kinds. To expand the repertoire of accessible biochemical properties, some proteins undergo covalent modifications once the correct tertiary fold has been attained. In this research, protein self-modification mechanisms are investigated that involve spontaneous oxidation reactions of intrinsic amino acid residues. In a group of fluorescent proteins, the energy barrier to the transfer of electrons from the protein to oxygen is lowered substantially without the aid of metal ions, a process that is not well understood. This project employs green fluorescent protein as a model system to elucidate the nature of a slow oxidation reaction that is triggered by the protein fold and is essential in the formation of an intrinsic fluorophore. Broader Impact. This research will emphasize the development of human resources and novel curricular materials. To better integrate research and education, undergraduate and graduate students will be trained in interdisciplinary methods that are in high demand in modern biotechnological and biomedical research. Outreach activities will provide summer research internships to lecturers at teaching colleges.
