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Pharmacy and Pharmaceutical Sciences

Reuben J. Peters

2002

Diterpenes

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Abietadiene Synthase Catalysis:  Conserved Residues Involved In Protonation-Initiated Cyclization Of Geranylgeranyl Diphosphate To (+)-Copalyl Diphosphate, Reuben J. Peters, Rodney B. Croteau Feb 2002

Abietadiene Synthase Catalysis:  Conserved Residues Involved In Protonation-Initiated Cyclization Of Geranylgeranyl Diphosphate To (+)-Copalyl Diphosphate, Reuben J. Peters, Rodney B. Croteau

Reuben J. Peters

Abietadiene synthase catalyzes two sequential, mechanistically distinct cyclization reactions in the formation of a mixture of abietadiene double bond isomers as the committed step in resin acid biosynthesis. Each reaction is carried out at a separate active site residing in a structurally distinct domain, and the reactions are kinetically separable. The first cyclization reaction is initiated by protonation of the terminal double bond of the universal diterpene precursor, geranylgeranyl diphosphate. The pH dependence of the overall reaction is consistent with an acid-base catalytic mechanism, and a divalent metal ion plays a role in this reaction probably by binding the diphosphate …