Terpenoid cyclases: design and function of electrophilic catalysts.
Terpenoid cyclases catalyse the cyclization of the universal acyclic precursors geranyl and farnesyl diphosphate to monoterpenes and sesquiterpenes, respectively. All such cyclases investigated to date are operationally soluble, moderately lipophilic proteins of relative molecular weight 40,000-100,000, requiring no cofactors other than a divalent metal, usually Mg2+ and occasionally Mn2+. The focus of most work has been on the mechanisms of the cyclization reactions themselves. It is currently proposed that the cyclase binds the acyclic substrate in a suitable conformation and initiates the cyclization by ionization of the labile allylic diphosphate moiety. The use of stereospecifically labelled substrates and analysis of the sites of labelling in the derived cyclization products has allowed the proposal of detailed cyclization mechanisms. Further insight into the architecture and function of the cyclase active site has come from the study of substrate and intermediate analogues designed to act as potential inhibitors or anomalous substrates of the normal cyclization reaction. Progress has also been made on the cloning of the relevant structural genes for sesquiterpene cyclases. This has led to new insights into the basic requirements for cyclase catalysis and specificity.
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Department of Chemistry, Brown University, Providence, RI 02912.
D000595:Amino Acid Sequence; D002384:Catalysis; D004583:Electrons; D007477:Ions; D008956:Models, Chemical; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000737:chemistry*
D007477:Ions; D013729:Terpenes