Crystal structure of pentalenene synthase: mechanistic insights on terpenoid cyclization reactions in biology.
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.
Lesburg
C A
CA
Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA.
Zhai
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G
Cane
D E
DE
Christianson
D W
DW
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
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