The crotonase superfamily: Divergently related enzymes that catalyze different reactions involving acyl coenzyme A thioesters

Synergistic investigations of the reactions catalyzed by several members of an enzyme superfamily provide a more complete understanding of the relatio nships between structure and function than is possible from focused studies of a single enzyme alone. The crotonase (or enoyl-CoA hydratase) superfami ly is such an example whereby members catalyze a wide range of metabolic re actions bur share a common structural solution to a mechanistic problem. So me enzymes in the superfamily have been shown to display dehalogenase, hydr atase, and isomerase activities. Others have been implicated in carbon-carb on bond formation and cleavage as well as the hydrolysis of thioesters. Whi le seemingly unrelated mechanistically, the common theme in this superfamil y is the need to stabilize an enolate anion intermediate derived from an ac yl-CoA substrate. This apparently is accomplished by two structurally conse rved peptidic NH groups that provide hydrogen bonds to the carbonyl moietie s of the acyl-CoA substrates and form an "oxyanion hole".