Free Radical Enzymes harness Radical Reactivity
Portland, Ore. — Unlocking the secrets of free radical metalloenzymes is the goal of a $1 million, four-year grant from the National Institutes of Health to James Whittaker, Ph.D., associate professor of biochemistry and molecular biology at the OGI School of Science & Engineering (www.bmb.ogi.edu/BMB/whittaker.html).
Free radical metalloenzymes are enzymes that combine metals, like copper, with redox-active protein sidechains containing unpaired electrons. Free radicals are very reactive and in biology are often perceived as "bad, blamed for carcinogenesis and aging. However, some free radical enzymes are essential to life.
Whittaker and his partner, OGI senior research associate Mei Whittaker (also his wife), are concentrating on free radical copper metalloenzymes such as galactose oxidase and glyoxal oxidase. Galactose oxidase, for example, combines the reactivity of a free radical ligand with a redox-active metal center in a unique catalytic complex: the free radical-coupled copper active site. Galactose oxidase's novel structure is the basis for a new family of enzymes that the Whittakers discovered in 1988.
Using a variety of techniques ranging from fermentation biotechnology to protein biochemistry and advanced spectroscopy, the Whittakers are producing large quantities of pure enzyme in their lab and then examining its structure and catalytic mechanism in atomic and electronic detail. Understanding the structural origins of catalytic function for these metalloenzymes may someday help researchers develop improved screening tools for cancer and other metabolic disorders, contributing to human longevity.