Structure of trichodiene synthase from Fusarium sporotrichioides provides mechanistic inferences on the terpene cyclization cascade

The x-ray crystal structure of recombinant trichodiene synthase from Fusari um sporotrichioides has been determined to 2.5-Angstrom resolution, both un liganded and complexed with inorganic pyrophosphate. This reaction product coordinates to three Mg2+ ions near the mouth of the active site cleft. A c omparison of the liganded and unliganded structures reveals a ligand-induce d conformational change that closes the mouth of the active site cleft. Bin ding of the substrate farnesyl diphosphate similarly may trigger this confo rmational change, which would facilitate catalysis by protecting reactive c arbocationic intermediates in the cyclization cascade. Trichodiene synthase also shares significant structural similarity with other sesquiterpene syn thases despite a lack of significant sequence identity. This similarity ind icates divergence from a common ancestor early in the evolution of terpene biosynthesis.