Structure and mechanism of the diterpene cyclase ent-copalyl diphosphate synthase

The structure of ent-copalyl diphosphate synthase reveals lthree alpha-helical domains (alpha, beta and gamma), as also observed in the related diterpene cyclase taxadiene synthase. However, active sites are located at the interface of the beta gamma domains in ent-copalyl diphosphate synthase but exclusively in the alpha domain of taxadiene synthase. Modular domain architecture in plant diterpene cyclases enables the evolution of alternative active sites and chemical strategies for catalyzing isoprenoid cyclization reactions.