title: Crystal structure of pentalenene synthase: mechanistic insights on terpenoid cyclization reactions in biology.
abstract: The crystal structure of pentalenene synthase at 2.6 angstrom resolution reveals critical active site features responsible for the cyclization of farnesyl diphosphate into the tricyclic hydrocarbon pentalenene. Metal-triggered substrate ionization initiates catalysis, and the alpha-barrel active site serves as a template to channel and stabilize the conformations of reactive carbocation intermediates through a complex cyclization cascade. The core active site structure of the enzyme may be preserved among the greater family of terpenoid synthases, possibly implying divergence from a common ancestral synthase to satisfy biological requirements for increasingly diverse natural products.
authors.affiliation: Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Lesburg
authors.forename: G
authors.initials: G
authors.lastname: Zhai
authors.forename: D E
authors.initials: DE
authors.lastname: Cane
authors.forename: D W
authors.initials: DW
authors.lastname: Christianson
mesh_terms: D019883:Alkyl and Aryl Transferases; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D003500:Cyclization; D003517:Cyclopentanes / Q000138:chemical synthesis / Q000737:chemistry; D051228:Geranyltranstransferase; D019753:Intramolecular Lyases; D007535:Isomerases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011106:Polyisoprenyl Phosphates / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012717:Sesquiterpenes; D013302:Streptomyces / Q000201:enzymology*; D014166:Transferases / Q000737:chemistry / Q000378:metabolism
chemical_list: D003517:Cyclopentanes; D011106:Polyisoprenyl Phosphates; D011994:Recombinant Proteins; D012717:Sesquiterpenes; C024646:pentalenene; C004808:farnesyl pyrophosphate; D014166:Transferases; D019883:Alkyl and Aryl Transferases; D051228:Geranyltranstransferase; D007535:Isomerases; D019753:Intramolecular Lyases; C048278:farnesylpyrophosphate cyclase