Protein design - now with metals!

Computationally-designed zinc-containing enzymes that can degrade molecules that are similar in structure to the nerve agent sarin are reported online this week in Nature Chemical Biology. Rational design of proteins has made important progress in recent years, identifying protein sequences with new protein folds and new enzyme activities. However, little attention has been paid to integrating metals into these systems. The incorporation of metals illustrated in this work - capable of catalyzing a wide variety of unusual reactions - should greatly broaden the reactions that are possible in protein design.David Baker and colleagues survey a wide number of known zinc-containing enzymes to identify 12 that have shapes that could be redesigned for their new reaction. They found that one of these enzymes did show some activity in breaking apart an organophosphate molecule. Further engineering by the team, guided in part by a crystal structure of the new enzyme, led to a successful enzyme.