Managing and manipulating carbocations in biology: terpenoid cyclase structure and mechanism

Terpenoid cyclases catalyze remarkably complex cyclization cascades that ar e initiated by the formation of a highly reactive carbocation in a polyisop rene substrate. Recent crystal structures of terpenoid cyclases show how th ese enzymes provide a template for binding and stabilizing the flexible sub strate in the precise orientation required for catalysis, trigger carbocati on formation, chaperone the conformations of the reactive carbocation inter mediates through a unique cyclization sequence, and sequester and stabilize carbocations from premature quenching. Notably, terpenoid cyclases and cat alytic antibodies have converged to similar chemical and structural strateg ies for managing highly reactive carbocations in polyisoprene cyclization c ascades.