Our research employs a broad range of biochemical, biophysical and molecular biology approaches to elucidate enzyme mechanisms, protein structure-function relationships, mechanisms of posttranslational modification of proteins, and biological energy metabolism.A general goal of this research is to describe how specific enzymes control the transfer of reactive electrons and the activation of molecular oxygen, while minimizing oxidative damage. The ability to do this is central to cell development, health and survival. Reactive oxygen species and free radicals are produced as by-products of biological electron transfer and oxygen metabolism. Defining the mechanisms of long range electron transfer reactions will enhance our understanding of the fundamental processes of respiration and intermediary metabolism at the molecular level. An understanding of the mechanisms of control of biological electron transfer reactions will provide insight into how defective protein electron transfer leads to production of free radicals and reactive oxygen species which cause non-specific oxidative damage to cell components that is associated with mitochondrial myopathies, oxidative stress, many disease states, and aging.Free radicals and reactive oxygen species are also required for, and used productively in biosynthetic processes. An example of such a process is the biosynthesis of protein-derived cofactors. Recent advances in enzymology, structural biology and protein chemistry have documented that catalytic and redox-active prosthetic groups may be derived from posttranslational modification of amino acid residues of proteins. These protein-derived cofactors typically arise from oxygenation of aromatic residues, covalent cross-linking of amino acid residues, or cyclization or cleavage of internal amino acid residues. Studies of the biosynthesis and function of protein-derived cofactors are revealing novel chemical mechanisms for both the biosynthesis of the cofactors and the reactions that they subsequently catalyze. The characterizations of protein-derived cofactors and their mechanisms of biosynthesis introduces a new dimension to our current views about protein evolution and protein structure-function relationships, and provides insight for protein engineering strategies to introduce new functional groups into proteins.