CRYSTAL-STRUCTURE OF PENTALENENE SYNTHASE - MECHANISTIC INSIGHTS ON TERPENOID CYCLIZATION REACTIONS IN BIOLOGY

The crystal structure of pentalenene synthase at 2.6 angstrom resoluti on reveals critical active site features responsible for the cyclizati on of farnesyl diphosphate into the tricyclic hydrocarbon pentalenene. Metal-triggered substrate ionization initiates catalysis, and the alp ha-barrel active site serves as a template to channel and stabilize th e conformations of reactive carbocation intermediates through a comple x cyclization cascade. The core active site structure of the enzyme ma y be preserved among the greater family of terpenoid synthases, possib ly implying divergence from a common ancestral synthase to satisfy bio logical requirements for increasingly diverse natural products.