1. Switching on a Nontraditional Enzymatic BaseDeprotonation by Serine in the ent-Kaurene Synthase from Bradyrhizobium japonicum
- Author
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Jia, Meirong, Zhang, Yue, Siegel, Justin B, Tantillo, Dean J, and Peters, Reuben J
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,acid-base catalysis ,biosynthesis ,enzymology ,natural products ,terpene synthases ,Inorganic Chemistry ,Organic Chemistry ,Chemical Engineering ,Industrial biotechnology ,Organic chemistry ,Physical chemistry - Abstract
Terpene synthases often catalyze complex carbocation cascade reactions. It has been previously shown that single residue switches involving replacement of a key aliphatic residue with serine or threonine can "short-circuit" such reactions, presumed to act indirectly via dipole stabilization of intermediate carbocations. Here a similar switch was found in the structurally characterized ent-kaurene synthase from Bradyrhizobium japonicum. Application of a recently developed computational approach to terpene synthases, TerDockin, surprisingly indicates direct action of the introduced serine hydroxyl as a catalytic base. Notably, this model suggests alternative interpretation of previous results, and potential routes towards reengineering terpene synthase activity more generally.
- Published
- 2019