Selenium is a required micronutrient for mammals, birds, and bacteria. Selenium is essential for the proper function of the immune system, thyroid hormone activation, and for cellular defense against oxidative damage. Selenium deficiencies also cause cardiomyopathies in humans. Selenium is essential for health because the synthesis and activity of certain enzymes require the selenium amino acid, selenocysteine. The bacterium Escherichia coli produces a selenocysteine-containing enzyme, formate dehydrogenase, when grown under anaerobic conditions. We have used this as an easily manipulable model system for analyzing some of the unique biochemical properties of selenocysteine. We have purified formate dehydrogenase and studied its biochemical properties. The selenocysteine of formate dehydrogenase has been replaced with cysteine by site-directed mutagenesis, and the resulting mutant enzyme provides a sulfur analog of a selenoprotein. Comparison of the properties of the wild - type and mutant enzymes demonstrates that sulfur is able to replace selenium at this catalytic center, but the resulting mutant enzyme has greatly diminished catalytic activity. The tremendous difference in catalytic properties helps to explain the evolutionary conservation of selenocysteine as an essential protein component. Elucidation of selenium's biochemical properties would allow a greater appreciation of its essential dietary role. Further, with an understanding of the mechanism of selenocysteine incorporation into protein, one could direct the mutagenesis of a protein such that selenocysteine replaces cysteine. Such protein engineering could alter the catalytic properties of many enzymes.
